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Chromatin organizes itself into 3D ‘forests’ in single cells

Chromatin organizes itself into 3D ‘forests’ in single cells

A single cell contains the genetic instructions for an entire organism. This genomic information is managed and processed by the complex machinery of chromatin — a mix of DNA and protein within chromosomes whose function and role in disease are of increasing interest to scientists.

A Northwestern University research team — using mathematical modeling and optical imaging they developed themselves — has discovered how chromatin folds at the single-cell level. The researchers found chromatin is folded into a variety of tree-like domains spaced along a chromatin backbone. These small and large areas are like a mixed forest of trees growing from the forest floor. The overall structure is a 3D forest at microscale.

szleifer chromatin forest
Igal Szleifer

Chromatin is responsible for packing DNA into the cell nucleus. In humans, that’s about six feet of DNA in each cell. The new work suggests that chromatin is more structured and hierarchical in single cells than previously thought. Learning how chromatin correctly operates will help scientists understand what goes wrong with it in cancer and other diseases.

“By integrating theoretical and experimental work, we have produced a new chromatin folding picture that helps us see how the 3D genome is organized at the single-cell level,” said Igal Szleifer, the Christina Enroth-Cugell Professor of Biomedical Engineering at Northwestern’s McCormick School of Engineering. He co-led the research team with Vadim Backman.

Details of the interdisciplinary study were published today (Jan. 10) in the journal Science Advances.

“If genes are the hardware, chromatin is the software,” said Backman, the Walter Dill Scott Professor of Biomedical Engineering and director of the Center for Physical Genomics and Engineering. “If the structure of chromatin changes, it can alter the processing of the information stored in the genome, but it does not alter the genes themselves. Understanding chromatin folding holds the key to understanding how cells differentiate and how cancer happens.”

backman chromatin forest
Vadim Backman

Advances in genomic, imaging and information technologies are just beginning to enable scientists to better understand how chromatin works. The Northwestern researchers used a Partial Wave Spectroscopic (PWS) microscope, optical imaging developed by Backman and colleagues, to peer deep into live cells and “sense” alterations in chromatin packing. They also used electron imaging.

“Our paradigm-shifting picture of chromatin folding is an important missing piece in the holistic view of genomic structure,” said Kai Huang, the study’s first author. Huang is a postdoctoral fellow in Backman’s research group. “The results should inspire new strategies to fight cancer.”

The research was supported by the National Science Foundation and the National Cancer Institute at the National Institutes of Health.

The paper is titled “Physical and data structure of 3D genome.” The corresponding authors are Szleifer, Backman and Huang.

Backman also is professor of medicine and of biochemistry and molecular genetics at the Feinberg School of Medicine, program leader in cancer and physical sciences at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University and a member of the Chemistry of Life Processes Institute.

Original story was published on January 10, 2020 in Northwestern Now by Megan Fellman.

Main image: A 3D forest of chromatin predicted by the researchers’ model. Tree domains are colored from red to green according to their sizes.

Both Igal Szleifer and Vadim Backman are members of the Chemistry of Life Processes Institute.

CLP Spills the Tea with Faculty Members to Mark 150 Years of Women at Northwestern

CLP Spills the Tea with Faculty Members to Mark 150 Years of Women at Northwestern

In light of the University’s year-long celebration of ‘150 Years of Women at Northwestern’, Chemistry of Life Processes Institute will host first of three ‘CLP Spills the Tea‘ events on January 15 at 4:00 p.m. on the Evanston campus. The program will include tea, cookies, and conversation with four prominent Chemistry of Life Processes Institute scientists at the top of their game.

The discussion will cover career highs and lows; navigating gender-based challenges; opening doors to create greater access; juggling work/family balance; and the people who inspired them to aim high and reach for their goals.

Speakers:

Teri Odom, Charles E. and Emma H. Morrison Professor of Chemistry; Chair, Department of Chemistry, Weinberg College of Arts & Sciences

Monica Olvera de la Cruz, Lawyer Taylor Professor of Materials Science and Engineering; Professor of Chemistry, Chemical and Biological Engineering, Physics and Astronomy, McCormick School of Engineering

Heather Pinkett, Associate Professor of Molecular Biosciences, Weinberg College of Arts & Sciences

Danielle Tullman-Ercek, Associate Professor of Chemical and Biological Engineering, McCormick School of Engineering

Moderator:

Sheila Judge, Senior Director for Research, Education and Administration, Chemistry of Life Processes Institute

The program will be held in Cohen Commons, Northwestern University, Room L482, fourth floor north, in the Technological Institute, 2145 Sheridan Road, Evanston, IL.

RSVP REQUESTED

Disorderly DNA Helps Cancer Cells Evade Treatment

Disorderly DNA Helps Cancer Cells Evade Treatment

Each cell in the human body holds a full two meters of DNA. In order for that DNA to fit into the cell nucleus — a cozy space just one hundredth of a millimeter of space — it needs to be packed extremely tight.

A new Northwestern University study has discovered that the packing of the three-dimensional genome structure, called chromatin, controls how cells respond to stress. When the chromatin packing is heterogenous and disordered, a cell demonstrates more plasticity. When the packing is neat and orderly, a cell cannot respond as easily to outside stressors.

This discovery comes with both good and bad news.

The bad news: This means cancer cells with disordered packing are more likely to adapt to and evade treatments, such as chemotherapy. The good news: Now that researchers have this information, they can develop new cancer therapies that target chromatin packing. By inhibiting cancer cells’ ability to adapt, those cells become more vulnerable to traditional treatments.

backman chromatin

Vadim Backman

“Cancer cells are masters of change,” said Northwestern’s Vadim Backman, who co-led the research. “They have to continuously adapt to evade the immune system, chemotherapies or immunotherapies. Abnormal chromatin packing drives cancer cells’ ability to do this.”

The study was published today (Jan. 8) in the journal Science Advances.

Backman is the Walter Dill Scott Professor of Biomedical Engineering in Northwestern’s McCormick School of Engineering, director of the Center for Physical Genomics and Engineering and the associate director for Research Technology and Infrastructure at the Robert H. Lurie Comprehensive Cancer Center at Northwestern University. He co-led the work with Igal Szleifer, the Christina Enroth-Cugell Professor of Biomedical Engineering, in McCormick.

Made of DNA, RNA and proteins, chromatin determines which genes get suppressed or expressed. In the case of cancer, chromatin can regulate expression of the genes that enable cells to become resistant to treatment.

“Genes are like hardware, and chromatin is software,” Backman said. “And chromatin packing is the operating system.”

szleifer chromatin

Igal Szleifer

“The genome has been sequenced, and techniques, such as CRISPR, now allow researchers to edit a cell’s ‘hardware,’” Szleifer added. “The role of chromatin structure on gene expression, however, has remained a scientific mystery.”

To help solve this mystery, Backman, Szleifer and their teams combined nanoscale imaging technologies with molecular dynamics modeling to analyze nanoscale alterations in chromatin packing structure.

Using data from The Cancer Genome Atlas, they analyzed cells from patients with colorectal, breast and lung cancers for markers of transcriptional plasticity. The researchers also used Partial Wave Spectroscopic (PWS) microscopy, which previously was developed in Backman’s laboratory, to examine chromatin in living cells in real time.

The researchers discovered an inverse relationship between patient survival and the plasticity of tumor cells. Backman says that chromatin engineering opens the door for a new class of cancer therapies, which could re-wire cells’ “operating systems” to make them less plastic.

“We found that transcriptional plasticity and chromatin packing alterations are an important marker, which is indicative of how a cancer patient may respond to anti-cancer therapies, such as chemotherapy,” said Ranya Virk, the paper’s first author. “This can be translated into a new method of predicting outcomes of cancer therapy.”

The study, “Disordered chromatin packing regulates phenotypic plasticity,” was supported by the National Science Foundation (award number EFMA-1830961) and the National Institutes of Health (award numbers R01CA228272, R01CA225002, U54CA193419 and T32GM008152). Northwestern Ph.D. candidates Ranya Virk, Wenli Wu and Luay Almassalha were the paper’s co-first authors.

Original story published in Northwestern Now by Amanda Morris.

Vadim Backman and Igal Szleifer are Chemistry of Life Processes Institute Faculty members. Their work was supported, in part, by the Chicago Region Physical Sciences-Oncology Center, the product of a partnership between the Northwestern Chemistry of Life Processes Institute and the Robert H. Lurie Comprehensive Cancer Center.  Thomas O’Halloran, PhD, is the Center’s principal investigator.

Budding Scientist Flourishes at Northwestern

Budding Scientist Flourishes at Northwestern

Growing up in Michigan, Isabella (Bella) Borgula, a senior at Northwestern, developed a passion for chemistry earlier than most kids.

“One thing that I distinctly remember is that my dad would buy me GIANT Microbes®, these little stuffed animals of viruses and bacteria,” Borgula said. “I thought they were the coolest thing; I kept the tags on them. I think that’s where my interest in the smallest elements of science started. Not a typical thing that you buy your child.”

In addition to her father Thomas Borgula, ‘89, Borgula’s high school chemistry teacher, also fueled her interest in science.

“I fell in love with chemistry in high school. I had a wonderful chemistry class with my teacher Ms. Webb. Her enthusiasm for chemistry was palpable, and it was very easy to catch onto,” Borgula said. “We talked a lot about the applications of chemistry and I just knew that I needed to keep going in that field.”

With college decisions looming, Borgula signed up for Northwestern’s Modern Cosmology In Focus Seminar led by Dr. Andrew Rivers, in her junior year to get a better feel for the college experience.

“We went into a three hour lecture each day with a group of 20 passionate juniors in high school and we’d talk about cosmology, physics, the origins of the universe, and a bunch of really nerdy things,” says Borgula. “I decided I need to have more of this community in my life and knew I needed to apply to Northwestern. These are the people I wanted to be surrounded by—people that will encourage my passion for science and provide this supportive, constructive environment.”

Her father Tom Borgula’s own experience at Northwestern also influenced the Borgula’s decision to attend. An exceptional baseball player, Bella’s father was recruited by a number of top universities, including Northwestern. From the moment he arrived on campus, he noticed something different about the students.

“I went on a recruiting visit to Northwestern and just felt like I fit in. The students seemed much more serious about academics like me,” her father said.  “The athletic department was also more serious. Whereas the other schools? You were there to play sports.”

After graduation, Borgula’s dad was drafted by the Chicago White Sox and played a year in the minor league.  Later, he completed his DDS degree and orthodontics residency, moved back to Michigan, and got married. In 1997, he began his orthodontics practice and started his family of four with wife Terry.

From Collecting GIANT Microbes® to Chemistry Major

Borgula and her father Thomas Borgula, ‘89

At Northwestern, Borgula enrolled in general chemistry, eager to try research.

“I was a little apprehensive at first to go Northwestern because I thought that I wouldn’t be able to compete with other students for research positions. Everyone knows Northwestern is such a good school—especially the chemistry department. It’s world renowned.” Borgula said.  “I wasn’t sure if I was cut out for it, so I spent freshman year building up my confidence.”

In the fall of 2017, Borgula reached out to Thomas O’Halloran, the Morrison Professor of Chemistry and Founding Director of Chemistry of Life Processes Institute (CLP), who urged her to apply for the Institute’s Lambert Fellowship. A highly competitive two-year award for rising sophomores and juniors majoring in Chemistry, the Fellowship provides funding for hands-on laboratory research, training in how to use the equipment in CLP-affiliated core facilities, and stipends for supplies, fees and travel to academic conferences. The award also includes a mentoring plan that allows fellows to work alongside CLP faculty members and postdoctoral and graduate students who share their interests.

Borgula and her advisor Thomas O’Halloran, the Charles E. and Emma H. Morrison Professor of Chemistry and Molecular Biosciences

“I wasn’t sure if I was going to be able to compete for such a lucrative fellowship, but I spent a lot of time writing my draft and collecting feedback from people in my lab. I was fortunate enough to be given the Fellowship,” Borgula said.

O’Halloran’s groundbreaking zinc sparks research initially drew Borgula to his lab. In 2014, the group discovered that the female mammalian egg releases a dazzling burst of zinc during fertilization that passes through the protein coat and surrounds the egg. This crucial process prevents more than one sperm from fertilizing the egg.

“When a sperm is inseminated into the female reproductive track, it is developmentally mature, but it’s not yet activated for fertilization. To become capable of fertilization, it must undergo two processes. First is capacitation, where it’s starts moving a little faster, and then it undergoes the acrosome reaction,” Borgula said. “The acrosome is a little organelle that sits on the apex of the sperm head and contains a number of proteolytic enzymes that break down proteins in the female reproductive tract. My project focuses on the acrosome reaction, which is absolutely critical for fertilization.”

Lambert Fellowship Opens Doors from Switzerland to Argentina

The Lambert Fellowship, underwritten by the Institute’s generous board members, enabled Borgula to attend the International Conference on Biological Inorganic Chemistry in Switzerland last summer a rare opportunity for an undergraduate.  She registered and submitted her abstract to give a poster presentation, but, to her surprise, was selected for something even more prestigious.

“I got an email from the board saying that I had been selected to give flash presentation in front of the entire conference,” Borgula said. “It was one of the most exciting, thrilling, terrifying things I’ve ever done. Having the platform to share my passion for science with so many people that are also passionate about science is something I’ve always dreamed of.”

Her biggest fan, however, was her father who accompanied her on the trip and sat through all of the talks, in addition to Bella’s.

Borgula at the International Conference on Biological Inorganic Chemistry in Switzerland

“My dad has been such a supportive role throughout my career as a student, and now as a budding scientist,” says Borgula. “I dragged him through all the airports and it was an opportunity for him to see how much I’ve grown as an individual in college. Back at home, I’m hanging out with my family and relaxed, but he got to see me navigating cities and airports and being the adult that I’ve become while I’ve been away from home.”

The speaking opportunity elevated Borgula’s profile at the conference and attracted a number of scientists to her poster presentation about the acrosome reaction of sperm.

“Bella was up there with a bunch of graduate students doing her flash poster presentation and, to the credit of Northwestern, she sounded just like any other graduate student,” Bella’s father said. “Dr. O’Halloran has been a great PI for her. I got to meet him there and a few of his previous students who are now professor at other schools. He’s patient and treats Bella like a graduate student which has given her a lot of confidence.”

Last summer, CLP also made possible the opportunity for Borgula to travel to Argentina to conduct research in the lab of Mariano Buffone, a world-leading expert in the molecular mechanisms of mammalian sperm during fertilization.

Borgula with Jamaica Schiavi from the Buffone Lab at the Instituto de Biología y Medicina Experimental in Buenos Aires, Argentina

“His lab has a mouse line that makes it much easier for us to analyze the acrosome reaction of massive number of sperm. It was an amazing opportunity to get data more quickly, and it raised a bunch of other questions about my project and procedure and where we’re going next,” Borgula says.

Borgula intends to continue investigating the interface between biochemistry and inorganic chemistry in graduate school for which she is currently applying.

“When I first stumbled upon the CLP web page, I was amazed by how many different kinds of scientists there were,” says Borgula. “Growing up as a researcher in CLP has influenced my perspectives on what a successful researcher should be and taught me the importance of collaboration. Exposure to all of these different perspectives has been extremely influential in my growth and development as a scientist.”

The appreciation goes both ways.

“Having undergraduate students as passionate as Bella in the lab is one of the reasons why I went into academic research,” says O’Halloran. “She brings this incredible enthusiasm for chemistry and biology and a willingness to try any kind of experiment, no matter how difficult. It’s pretty rare for an undergraduate to have accomplished so much at this stage and it bodes well that she will have an outstanding career in biomedical research.”

by Lisa La Vallee

Feature image (top of page): Undergraduate Isabella Borgula gives a flash poster presentation at the International Conference on Biological Inorganic Chemistry in Switzerland.

Two Generations Find Their Way at Northwestern

Two Generations Find Their Way at Northwestern

Like many first-year students, Myung Shin ’87 was undecided about his major when he arrived at Northwestern. He was initially drawn to political science, but his parents had other plans.

“They wanted me to go to medical school, but I didn’t know if that was right for me,” said Shin, who is a member of the University’s Chemistry of Life Processes Institute (CLP) Executive Advisory Board and serves as executive director and head of early discovery genetics at Merck & Co. “I always liked and did well in science, so I enrolled in the biochemistry molecular biology and cell biology program.”

Two years later, Shin decided to try research and asked Professor Rick Morimoto about opportunities in his lab. Morimoto, who had no space, suggested reaching out to Thomas O’Halloran, a new assistant professor with a joint appointment in chemistry and molecular biosciences. O’Halloran welcomed Shin into his lab, where he found his true calling.

“Having a faculty member take the time to mentor me and allow me to set up his research lab was an unbelievable experience,” Shin said. “It truly changed my life and helped me find what I really wanted to do. What excited me most about research was the ability to ask new questions, find new ways of doing things, and break new ground.”

Shin continued to work in O’Halloran’s lab for a year after graduating from Northwestern, an experience that solidified his desire to attend graduate school. Six years later, he earned his PhD in molecular biology from the University of California, Berkeley. After completing a postdoctoral fellowship at Princeton University as a Jane Coffin Childs and HHMI Postdoctoral Fellow, Shin took a faculty position at Fox Chase Cancer Center in the cellular and developmental biology program. He joined Merck in 2004.

Today, Shin leads a unit at Merck that focuses on early discovery genetics. The department’s mission is to identify targets for drug discovery based on human genetics data. The group covers a number of different therapeutics areas, including cardiovascular and liver diseases; neurological diseases like Alzheimer’s and Parkinson’s disease; and age-related retinal diseases.

Shin also supports science and innovation at Northwestern as a member of the Chemistry of Life Processes Institute (CLP) Executive Advisory Board. CLP’s expansive, transdisciplinary approach and state-of-the-art facilities accelerate drug development and biomedical discovery at the University. O’Halloran is the Charles E. and Emma H. Morrison Professor of Chemistry, professor of molecular biosciences in the Weinberg College of Arts and Sciences, and the institute’s founding director.

While a student at Northwestern, Shin met his future wife, Pheodora Shin ’87, ’89 MD, who grew up in Skokie, Illinois. She is a pediatric anesthesiologist at Morristown Medical Center in New Jersey, where the couple settled down to raise their daughter Grace.

This fall, Grace entered Northwestern undecided about her major, just as her father had been three decades earlier. Like him, she is taking advantage of the University’s vast offerings to find her own calling.

Myung and Grace Shin, captured in the east atrium of Silverman Hall during festivities celebrating the past 10 years of innovation in the Chemistry of Life Processes Institute.

“I chose Northwestern because I felt it could give me a wide variety of options, so that no matter what I do, I would be well equipped with the resources here,” she said.

As Grace begins her Northwestern education, her parents remain active in the alumni community and contribute to their class scholarship funds for the Weinberg College of Arts and Sciences and Feinberg School of Medicine.

“Northwestern allowed us to grow as young adults and find our way,” Shin said. “My wife was not from a wealthy family and was a Pell Grant recipient. Northwestern offered her a path where she did not have a huge amount of student loans. One of the things that we commit to, along with supporting Chemistry of Life Processes Institute, is giving back to ensure as many people as possible from different backgrounds can benefit as we have from a Northwestern education.”

by Lisa La Vallee

 

 

2019 Chemistry of Life Processes Institute Discoveries and Impact

2019 Chemistry of Life Processes Institute Discoveries and Impact

This year, the Chemistry of Life Processes Institute celebrated a decade of transformative science. Since its debut in Silverman Hall in 2009, the Institute’s team science approach to integrating engineering, physics, chemistry, biology and medicine has led to unprecedented breakthroughs in biomedical research and the development of new drugs and diagnostics (see video).

CLP realized its vision in 2019 with numerous research collaborations among CLP’s 66 faculty members (7 new to the Institute this year), including:

CLP  advanced its mission to translate faculty innovations from the laboratory to the patient bedside with new partnerships and programs:

  • The Institute hosted a national investor summit in April that brought investors to campus to learn about high impact translational projects in CLP labs. Half of the presentations resulted in direct investor interest. Based on this success, a second ‘Biotech by the Lake’ event will be held in May 2020.
  • To help demystify the drug development process for Northwestern faculty and students, CLP Entrepreneur-In-Residence Bill Sargent wrote and published online the Beginner’s Guide to Academic Drug Development’.

Faculty innovations that have spun out from, or originated with, CLP are finding success in areas ranging from cancer treatment to agriculture:

The Institute’s growing portfolio of critical technologies have supported and opened up many new areas of investigation:

  • A $660K NIH Instrument Award to CLP’s Quantitative Bioelement Imaging Center will enable this core facility to acquire advanced instrumentation that will enable dynamic measurement of the metal content and their localization in cells from healthy and diseased tissues.

Looking to the future, the Institute continues to engage students in transdisciplinary research and translation.  CLP’s NIH-funded graduate training program and donor-funded undergraduate research programs have trained budding scientists like Viswajit Kandula, Ryan McClure and Jennifer Ferrer, to work across disciplinary silos to lead the next wave of scientific discovery.

by Lisa La Vallee

Innovative Plastic Upcycling Project Receives 2020 CLP Cornew Award

Innovative Plastic Upcycling Project Receives 2020 CLP Cornew Award

The rampant proliferation of plastic in the environment, one of the world’s most widely used materials, is a massive and growing concern.  Over the past 50 years, the world has produced 8 billion tons of plastic. Less than half is reused, or recycled into new items. The remainder has accumulated in landfills, oceans, and beaches, and found its way into our food chain and drinking water. If the trend continues, experts predict that by 2050 the ocean will contain more plastic waste (by weight) than fish.

Monica Olvera de la Cruz, Lawyer Taylor Professor of Materials Science and Engineering and Chemistry,  and Danielle Tullman-Ercek, Associate Professor of Chemical and Biological Engineering, are using a new Cornew Innovation Award from the Chemistry of Life Processes Institute (CLP) at Northwestern, to turn the tide on plastic through upcycling. The nascent process involves deconstructing plastic waste back into its basic molecular components, in an environmentally friendly way, with the goal of ultimately reducing the amount of single-use plastic produced globally.

Upcycling vs. Recycling

“Recycling implies a traditional process where plastic is melted down with whatever contaminants are there. The result is always lower quality plastic. Whereas, upcycling makes it just as good as the original product,” Olvera de la Cruz said.

One of the most common forms of plastic is polyethylene terephthalate (PET), a by-product of petroleum production. The basic building blocks of PET are ethylene glycol and terephthalic acid, organic molecules that combine to form polymer chains called monomers that are heated up and molded into products. PET is used to make synthetic fibers for clothing and textiles (polyester), as well as plastic bottles and containers. Designed to be durable and resistant to degradation, 96 percent of plastic bottles and containers made in the US are comprised of the PET with an average lifespan of 450 years.

The path to chemically upcycling of PET plastic waste opened up in 2016 when a team of Japanese researchers discovered a new species of bacteria, Ideonella sakaiensis, near a bottle-recycling facility. They found that these bacteria metabolize PET through secretion of a naturally occurring enzyme, or PETase, which degrades PET into its basic components.

The Challenge

Chemical upcycling poses a considerable scientific challenge. The current process requires significant energy, harsh chemicals, and is slow. Current PETase applications take days to a week to achieve measurable PET degradation.

The US Department of Energy’s Basic Energy Sciences Program held a Roundtable on Chemical Upcycling of Polymers last April to discuss new approaches to the problem. Olvera de la Cruz, is a member of the program’s Advisory Committee. The group identified several high priority opportunities for transforming plastic waste into higher value fuels, chemicals, and materials.

Inspired by the challenge, Olvera de la Cruz and Tullman-Ercek, who often cross paths in Silverman Hall, seized on the opportunity to collaborate. An expert in the statistical mechanics of soft materials, Olvera de la Cruz studies the interactions of polymers and the physical forces involved in breaking molecular bonds or optimizing polymers for various applications. Tullman-Ercek is skilled in optimizing enzymes for industrial purposes.

“We have these pieces of the process that we know,” Tullman-Ercek said. “If we could make the enzyme work better and faster, then we could make enzymatic degradation an industrially viable process.”

Funding from the CLP-Cornew Award has kick-started the collaborators’ multi-disciplinary project, which combines enzyme synthesis, plastic processing and modification, and random polymer design to enhance the enzymatic activity of PETase. Their approach involves encapsulating the enzyme with a polymer, a technique that originated in Olvera de la Cruz’s lab, to allow this water-based protein to align with, and act on, the oil-based the plastic molecules.  Encapsulation will also preserve enzyme activities under the elevated temperatures needed to quickly degrade PET.  In addition, Tullman-Ercek will genetically engineer the enzyme to create a modified enzyme that works more quickly on PET.

“We are going to direct its evolution towards what we need. It’ll happen faster than it would happen spontaneously in nature— a couple of years instead of a few decades,” Tullman-Ercek said. “We’re going to apply everything we learned with other enzymes and import that over, but we’re going to encounter challenges. So that’s, where our expertise comes in— overcoming whatever challenges arise.”

Data from these pilot experiments will be used to support the team’s application, with Northwestern University expert in polymers and collaborator John Torkelson, for various federal funding opportunities in this topic. Their long-term goal is to bring in other investigators to form a large, interdisciplinary team of engineers, chemists and biologists to direct their collective skills and knowledge towards tackling the global plastic problem.

“This project is a perfect example of how Institute researchers from very different areas work together to take on really big problems,” Thomas O’Halloran, Founding Director of Chemistry of Life Processes Institute, said. “I’m excited to see where their collaboration takes them.”

Danielle Tullman-Ercek and Monica Olvera de la Cruz and graduate students

About the CLP-Cornew Innovation Awards

CLP-Cornew Innovation Awards, made possible by the generosity of Chemistry of Life Processes Institute Executive Advisory Board (EAB) members, support promising interdisciplinary teams of CLP researchers in early stage development of high-risk, high-reward research projects with the potential to make significant impact.

Since 2008, the EAB has made 25 awards, worth a total of $1.07 million, to CLP faculty teams in pilot funding. Cornew Awards have resulted in 42 publications and more than $22 million in new external funding to advance these projects opening up critical areas of transdisciplinary research and resulting in discoveries that impact human health and disease.

by Lisa La Vallee

Featured image above (left-right): Monica Olvera de la Cruz and Danielle Tullman-Ercek

Chemistry of Life Processes Institute Welcomes Three Feinberg Faculty Members

Chemistry of Life Processes Institute Welcomes Three Feinberg Faculty Members

This fall, three members of Northwestern University’s Feinberg School of Medicine joined Chemistry of Life Processes Institute to strengthen opportunities for collaboration across disciplines and translation of their groundbreaking work. The Institute’s new members are Xiao-Nan Li, MD, PhD, Professor of Pediatrics (Hematology, Oncology, and Stem Cell Transplantation); Hande Özdinler, PhD, Associate Professor of Neurology; and Gabriel Rocklin, PhD, Assistant Professor of Pharmacology.

“It’s very exciting to have three members of the Feinberg faculty join the Institute,” says Thomas O’Halloran, Founding Director of the Institute. “Hande is doing brilliant work on understanding the molecular basis of neurodegenerative diseases like ALS and has formed some extraordinary collaborations with [CLP member] Rick Silverman.  Xiao-Nan brings a wealth of expertise in animal models of disease and development of new treatments. As a freshly minted faculty member, Gabe brings a whole repertoire of protein design tools that are based on molecular modeling and evolutionary principles.”

As Director of Pediatric Xenograft Modeling at the Manne Research Institute at Lurie Children’s Hospital, Xiao-Nan Li, an acclaimed cancer biologist, focuses on finding improved therapies for children with cancer. An expert in developing novel patient-derived orthotopic xenograft mouse models to understand tumor biology and identify new diagnostic and/or therapeutic targets, Li pioneered the development of clinically relevant and molecularly accurate animal models of pediatric brain tumors, and has developed 130 models of different brain tumor subtypes. Li will leverage his vast experience as the new Faculty Director of CLP’s Developmental Therapeutics Core where he will apply his expertise conducting comprehensive preclinical drug testing to establish rational for the initiation of clinical trials for promising research programs.

Li earned his PhD and MD, and completed his residency and fellowship at Suzhou Medical College/Soochow University in China. He completed a postdoctoral fellowship studying gene expression in cancer at Baylor College of Medicine.

“CLP offers me the best opportunity to collaborate with other outstanding investigators on multiple research topics of cancer research,” says Li. “It also enables me to contribute to Northwestern’s research community on preclinical development of new drugs and novel devices, and to facilitate the transition of novel discoveries to clinical applications.”

Hande Özdinler, PhD, is an Associate Professor at the Department of Neurology, Northwestern University, Feinberg School of Medicine.  She is also a member at the Mesulam Cognitive Neurology and Alzheimer’s Disease Center, the Robert H. Lurie Comprehensive Cancer Center, and the Les Turner ALS Center.

Özdinler received a Master’s degree in a program spanning chemical engineering and molecular biology and genetics; focusing on biotechnology. She received a PhD in Cell Biology, Anatomy and Neuroscience from Louisiana State University (LSU) Health Sciences Center.  She became a postdoctoral fellow at Neurosurgery Department of Massachusetts General Hospital-Harvard Medical School, prior to joining Northwestern as the founding director of the second Les Turner ALS Laboratory. Özdinler’s research is focused on understanding the cellular and molecular basis of selective vulnerability observed in neurodegenerative diseases.  The Özdinler lab primarily focuses on understanding the biology of upper motor neurons as well as the mechanisms that are responsible for their progressive degeneration, which is a hallmark in diseases such as amyotrophic lateral sclerosis, hereditary spastic paraplegia, and primary lateral sclerosis.  Her research program extends from biomarker discovery to development of drug verification platforms, and generation of mouse models of diseases to identification of novel targets for gene delivery approaches. Her work has been supported by National Institutes of Health, National Institute of Aging, and foundations, such as Les Turner ALS Foundation, ALS Association, and A Long Swim.

“I am thrilled to be a part of CLP’s collaborative environment where teams of top scientists solve complex problems. I believe this is just the beginning of great things to come,” says Özdinler.

Gabriel Rocklin, PhD received a BA in Biology-Chemistry and History from Claremont McKenna College and completed his PhD research at the University of California, San Francisco, supervised by Brian Shoichet and Ken Dill. With support from NSF and Department of Defense fellowships, he developed methods to improve the accuracy of molecular dynamics-based free energy calculations of protein-ligand binding. He completed his postdoctoral research with David Baker at the University of Washington as a Merck Fellow of the Life Sciences Research Foundation. There, he pioneered the use of large-scale protein design to understand protein biophysics. This work makes it possible to computationally design and experimentally characterize thousands of diverse proteins in parallel. In 2019, he started his independent group in Northwestern University’s Department of Pharmacology.

Rocklin is also a core member of Northwestern’s Center for Synthetic Biology. His group develops new high-throughput methods to improve computational protein design, understand protein biophysics, and design protein therapeutics.

“I’m very much at home in the interdisciplinary environment of CLP and am excited to make connections with the other CLP faculty,” says Rocklin. “I also hope that CLP can help move some of our basic science toward translation.”

by Lisa La Vallee

CLP Spinout Rounds Third Base with New Treatment for Metastatic Cancers and Fibrosis

CLP Spinout Rounds Third Base with New Treatment for Metastatic Cancers and Fibrosis

Veteran entrepreneurs and cofounders of Actuate Therapeutics, Inc., Daniel Schmitt and Andrew Mazar, PhD, are taking no chances with their lead clinical candidate 9-ING-41, a promising new treatment for advanced and drug-resistant cancers and select inflammatory diseases.

“Having done this many times before, we knew we needed a certain body of data to interest a potential pharma partner or investor,” said Mazar, the startup’s scientific co-founder. “All of our work was geared toward generating a proof of concept package.”

Mazar and Schmitt, President and CEO of Actuate, met at Northwestern as Entrepreneurs-In-Residence for Chemistry of Life Processes Institute’s (CLP) Center for Developmental Therapeutics (CDT) and the University’s Innovation and New Ventures Office (INVO), respectively. Schmitt was on the lookout for promising technologies to spin out. As EIR and managing director of CDT and faculty director of the center’s Developmental Therapeutics Core (DTC), Mazar led early academic drug discovery projects and developed commercialization strategies for the most promising programs. The core specializes in proof-of-concept study design and development of project packages for review by a pharmaceutical partner or investor. Through the generosity of the Baskes family philanthropy, CDT developed a repository of Patient Derived Xenografts (PDX) models used to assess new oncology drugs.

In 2015, DTC signed a cooperative research agreement with the University of Illinois-Chicago to run preclinical studies to test the efficacy of glycogen synthase kinase-3β (GSK-3β) inhibitors developed by UIC medicinal chemist Alan Kozikowski. GSK-3β is the gatekeeper of cell signaling pathways. Overexpression of this protein is found in Alzheimer’s disease, bipolar disorder, diabetes mellitus type II, and inflammatory conditions leading to fibrosis.  When dysregulated, it allows tumor cells to proliferate without control and is a marker of malignancy.   These characteristics make it an excellent target for drug therapies.

“The early work on this was really pointed towards neurodegenerative disease,” said Schmitt. Of all the compounds initially tested, the researchers found 9-ING-41 the most interesting in terms of specificity, potency, and brain penetration.

“One of the first models we looked at was primary malignant brain cancer (glioblastomas) and we saw this remarkable activity,” said Mazar. “When we started seeing this ability to restore sensitivity to chemotherapy that had been lost before, we got really excited.”  Collaborations between Chemistry of Life Processes Institute, CDT, and DTC faculty and staff, and other Northwestern investigators resulted in approximately fifteen publications.

The discovery prompted Schmitt and Mazar to spin out the technology and know-how from UIC and Northwestern in 2015 and form Actuate. They also secured initial funding to complete preclinical studies.

An early pioneer in using PDX models of cancers to screen drugs, CDT began in vivo and in vitro studies of 9-ING-41 to test its efficacy in combination with different chemotherapy drugs in drug-sensitive and drug-resistant carcinomas.  “The studies revealed significant increases in overall survival. The compounds were also well tolerated and demonstrated a favorable pharmacokinetic profile,” said Schmitt.

In March, 2016, the Federal Drug Administration granted 9-ING-41 an Orphan Drug Designation for treatment of glioblastoma. The following year, the company closed on $3.8 million in Series A funding for toxicology studies and the FDA further granted 9-ING-41 Orphan Drug Designation for the treatment of neuroblastoma in adults and children. In February 2018, the FDA accepted Actuate’s IND application for 9-ING-41, clearing the way for studies in patients with advanced cancers.

A Phase I/II clinical trial opened up in December, 2018, for treatment of chemo-resistant patients with advanced cancers, including glioblastoma, melanoma, pancreatic, appendix, breast and ovarian.  The trial was bolstered by an additional $21.7 million in Series B funding allowing Actuate to expand the clinical program.  Since initiation, more than 70 patients have been enrolled in the study.  A recent influx of $6.5 million will enable Actuate to open up two additional clinical trials, one in myelofibrosis and one in pediatric neuroblastoma, with collaborators at 20 different clinical sites in the US and Europe.

“We’ve dose-escalated 9-ING-41 in clinical trials through six different dose levels and we’ve had no serious adverse events. We’re getting very good data on clinical responses to the drug so far,” said Schmitt. “Metastatic disease has stabilized in a number of patients, including one that has, to date, shown a durable and complete response without recurrence.”

Alicia Löffler, PhD, the Executive Director of INVO, who recruited Dan Schmitt as EIR and helped broker the startup’s licensing deal and subsequent financing, also is very encouraged.  “Actuate’s progress is incredibly exciting,” says Löffler. ”Financial partners Kairos Ventures and others understand the importance and urgency in supporting early-stage innovations like 9-ING-41 that give new hope to millions of people living with the most aggressive forms of cancer.”

If things continue to go positively, Actuate aims to raise additional money to take the drug forward into registration, or to be acquired.

“I’ve been doing this for 30 years and what gets me up in the morning is knowing that we’re doing the right things to advance treatment for the patients,” said Schmitt. “That’s what we’re working for.”

by Lisa La Vallee

CLP Faculty Get Kellogg Crash Course on Entrepreneurship

CLP Faculty Get Kellogg Crash Course on Entrepreneurship

When it comes to running a business, even the most seasoned innovators, like Chemistry of Life Processes Institute member Richard Silverman (chemistry) who developed pregabalin, the chemical that became Lyrica®, the most financially successful drug ever to have come from a US academic institution, can use some tips. Thanks to the generosity of the Kellogg School of Management’s Center for Research in Technology & Innovation, last month, Silverman and several other CLP faculty members had the opportunity to learn from three of the nation’s foremost business innovation experts as special invitees to the center’s Practical Innovator Program.

Developed by Kellogg and CRTI faculty members James Conley, Thomas D. Kuczmarski and Mohanbir Sawhney, the one-day course teaches the practical skills of innovation and what it takes to develop a new product and introduce it to the marketplace.  Created as an exclusive learning opportunity for the top 100 finalists of the Chicago Innovation Awards, the program (a $2,500 value) was opened up to CLP faculty members for the very first time this year.=

After CLP’s Biotech by the Lake investor conference last March, Conley and O’Halloran began strategizing ways to capitalize on the synergies between the Institute and the Kellogg center.  The conference highlighted the translational work of CLP faculty members and presentations by Oppenheimer & Co., AbbVie, Genentech, and other industry leaders.

“The discipline of scientists here at Northwestern and, in particular, CLP, is to explore a knowledge frontier. They are the generators of innovation, creating new possibilities,” says Conley. “Kellogg faculty, on the other hand, are the executors— we know how to organize, package, sell, leverage, negotiate, market, and finance new offerings. The key is bringing these two groups together to make them conversant; it is a knowledge sharing opportunity. Turning that into some kind of commercial engine for the city is what the Practical Innovator Program tries to lay out.”

Startup and Management Wisdom

For Silverman, who recently launched Akava Therapeutics to bring forward the ongoing work in his lab, the program offered some essential pointers.

“The Kellogg instructors talked about what your team should look like with regard to a CEO and CSO and board members that can also chip in some money and are not there just for advice,” said Silverman. “They have to have specific expertise that you would need at each stage along drug development. You really have to be strategic about their talents and how they can advance what you are trying to do.”

The Silverman startup will be developing a new therapy for hepatocellular carcinoma (liver cancer), and Silverman and collaborator Hande Özdinler are aiming to begin toxicology studies for a new ALS drug that has produced very promising in vitro and in vivo data. Silverman also is in earlier stage development for Parkinson’s disease, Alzheimer’s disease, and melanoma.

“The course covered a lot of topics about entrepreneurship that just aren’t covered in our typical training,” said CLP member Julius Lucks (Chemical and Biological Engineering) who also attended the program.  “This was very directly related to me as we just launched our first startup out of the lab.”

Lucks’ startup, Stemloop, develops biological sensors using cell-free synthetic biology that leverages the natural ability of microorganisms to sense and respond to their environment.

“Courses like these really help build and nurture an environment of innovation at Northwestern,” said Lucks.

What struck CLP member Evan Scott (biomedical engineering) were the many synergies between starting a new company and running a lab.

“For professors running research labs, the management of people, money and resources occupy more than 75 percent of our time, but we don’t receive any official training on these subjects,” said Scott.  “How do I pick a fundable topic for my next grant? How do I best allocate my time and those of my research team? How can I find the right people? What I learned from the Kellogg instructors was that it is essentially the same for starting a small company.”

Veteran entrepreneur Thomas O’Halloran and founding director of CLP, also attended the program. After starting several biotech companies, including Viamet, Tactic Pharma, LLC, and its spinout Monopar Therapeutics, O’Halloran, understood many of the hurdles pointed out by the instructors.

“There are common pitfalls whether the innovator is creating a new food, energy supply, or application for your cell phone,” said O’Halloran. “Our colleagues in Kellogg are spectacular at honing in on the key characteristics of the most successful startups and innovators.”

One of the Institute’s key functions, said O’Halloran, is working with faculty, postdocs and graduate students from the time of inception of an idea to putting together the information needed to seek and secure funding.

“We try to be matchmakers and bring in the financial experts, the CEO, and CSO, to help move people’s companies forward. A finely-tuned course like this that lowers the hurdles to translating discoveries into society is exactly the type of information that our people are hungry for,” says O’Halloran.

by Lisa La Vallee

Main image: Thomas O’Halloran, Founding Director of CLP, James Conley, Clinical Professor of Innovation & Entrepreneurship, and CLP faculty members Evan Scott, Associate Professor of Biomedical Engineering, and Richard Silverman, Patrick G. Ryan/Aon Professor

CLP Introduces the ‘Beginner’s Guide to Academic Drug Development’

CLP Introduces the ‘Beginner’s Guide to Academic Drug Development’

Chemistry of Life Processes Institute (CLP) recently introduced a new resource for Northwestern University academic drug developers who wish to explore the necessary steps in developing and eventual marketing of promising drug therapies discovered in their labs.  The Beginner’s Guide to Academic Drug Development was developed by Dr. Bill Sargent, CLP’s Entrepreneur in Residence, drawing upon his 30-year career in the pharmaceutical industry and a decade in academic research and translation.

Hosted on the Center for Developmental Therapeutics home page, the Guide provides a detailed overview of the drug development process from discovery to filing an IND (Investigational New Drug Application) as well as links to Northwestern-specific experts.

“Drug development in an academic setting is very different from the pharmaceutical sector due to the lack of drug development experience and supporting infrastructure,” says Sargent.  “In the pharmaceutical industry, once we had identified a treatable target, we created a project team with people who had all the different drug development skills sitting around the table. Having gone through that process, I thought I could bring the most important parts of it back to academia to show how we move the product from an idea to a commercially viable product that can help the patient.”

The Guide provides drug developers with information about:

  • Northwestern policies and guidance
  • FDA’s structure and selected guidance documents for drug development
  • Scientific steps leading to identification of a patentable compound
  • Northwestern fee-for-service Scientific Cores and Centers of Excellence that can assist at each step
  • The patenting process, licensing and/or partnering process and Northwestern proprietary funding sources

In developing the Guide, Sargent incorporated feedback from the Institute’s transdisciplinary faculty and staff, managers of the University’s Core facilities, the Office of Research, the Innovation and New Ventures Office (INVO), NUCATS, Chicago Biomedical Consortium and other internal organizations involved in bringing innovations from the lab to society.  These stakeholders form what Sargent considers “a ‘virtual’ project team” for University drug developers.

“We’ve got some really creative ideas at Northwestern. Our scientists conduct years of research to understand a biological pathway and its role in a disease process.  Without this basic science, one would not know where to find a treatable target in the pathway,” says Sargent. “However, progressing from understanding basic pathways to identifying treatable targets takes a very long time, on average, about 10-15 years.”

As Entrepreneur-in-Residence, Sargent helps scientists determine whether a new discovery can address an unmet medical need in treating a specific disease process, and what other types of characteristics the drug will need in order to demonstrate efficacy in patients and to compete in the marketplace. He also helps to co-ordinate the research translation process. He hopes the Guide will stimulate researchers to press on in the development of promising treatments for clinical use.

“Many of Northwestern’s outstanding faculty in life scientists, chemistry, medicine, and engineering have phenomenal ideas about how to deliver drugs in novel ways, overcome toxicities, and target very specifically the disease tissue, or the tumor,” says Thomas O’Halloran, Founding Director of the Institute. “However, most of us do not have very much knowledge about how to develop our idea from theory to practice. This effort is an important first step.”

Sargent is available for consultation by appointment at bill.sargent@northwestern.edu.

by Lisa La Vallee

Chemistry of Life Processes Institute Celebrates 10 Years of Transformative Science

Chemistry of Life Processes Institute Celebrates 10 Years of Transformative Science

Chemistry of Life Processes Institute Celebrates 10 Years of Transformative Science

This fall marked the ten-year anniversary of Chemistry of Life Processes (CLP) Institute’s debut in The Richard and Barbara Silverman Hall for Molecular Therapeutics and Diagnostics. To celebrate, the Institute held a recognition program to thank its Executive Advisory Board members, faculty, staff, and students for their contributions.

“CLP has become a hotbed of interdisciplinary collaboration,” said Founding Director Thomas O’Halloran, “made possible by our committed faculty, outstanding students, talented research staff and administrators, supportive Vice President for Research, and the generosity of our Executive Advisory Board and donors.”

 

According to O’Halloran the Institute has experienced tremendous growth since moving into Silverman Hall in 2009.  The number of CLP faculty members increased 5-fold to more than 60, while Institute faculty developed four affiliated university center and eight core facilities that advance the research of hundreds of investigators across the region.  In addition, the Institute faculty teamed up to create an NIH-funded training program that has enabled graduate students to work seamlessly across disciplinary boundaries, learning new methods and instruments, and opening up new areas of discovery. 

During the recognition ceremony, O’Halloran thanked and presented a crystal award to each member of the Institute’s Executive Advisory Board for their ongoing support, including Stuart Cornew, who helped inspire the idea of CLP and for serving as first chair of Executive Advisory Committee, and Andrew Chan, Senior Vice President of Research Biology, Genentech, for shouldering the role of EAB chair and endowing the Institute’s Lambert Fellowship program that supports outstanding undergraduate researchers.

Richard B. Silverman, Patrick G. Ryan/Aon Professor; Professor of Chemistry, received award in recognition of his passion, dedication and generosity to the Institute.  O’Halloran also expressed appreciation for the contributions of administrative and core facility staff and scientists who received gift cards and special recognition from the core leaders.

 

“When CLP recently underwent external program review,” said O’Halloran, “the reviewers commented on the centrality of our affiliated centers and cores to the realization of the CLP mission and were deeply impressed by the extraordinary expertise and dedication of their research faculty, postdocs and technical staff.”

Last, O’Halloran gave special thanks to Sheila Judge, the Institute’s Senior Director for Research, Education and Administration, and Research Professor, whose leadership and dedication has enabled the Institute to flourish.

After the recognition event, attendees enjoyed a fall-themed lunch under a big tent just outside of Silverman Hall and were given CLP-branded t-shirts.

by Lisa La Vallee

 

Northwestern faculty elected to National Academy of Medicine

Northwestern faculty elected to National Academy of Medicine

Four Northwestern University professors have been honored with election to the National Academy of Medicine (NAM).

Joining more than 2,200 active NAM members are Dr. David Cella, Dr. Susan Quaggin, John A. Rogers and Catherine Woolley.

Rogers, who is already a member of the National Academy of Sciences and National Academy of Engineering, becomes one of just 25 people in history elected to all three academies.

Election into NAM, which was previously known as the Institute of Medicine, is one of the highest honors in the fields of health and medicine. The academy serves as a source of expertise by providing independent, evidence-based scientific and policy advice to inspire action across the private and public sectors regarding critical issues in health, medicine and science.

Since it was founded in 1970, NAM elects no more than 90 regular members and 10 international members annually based on professional achievement and a commitment to service and advancement in the fields.

David Cella

Cella is the chair and Ralph Seal Paffenbarger Professor of Medical Social Sciences in the Feinberg School of Medicine.

David Cella

As chair of an interdisciplinary department, Cella leads the development of transdisciplinary scientific collaborations and projects, and oversees its academic and research programs, financial operations, faculty affairs and program development. An international expert in the measurement and application of patient-reported outcomes in healthcare settings, his career spans nearly 860 publications and his research has helped advance the understanding of mechanisms and measurement of health and disease to improve patients’ quality of life.

“Election to NAM is the highest honor that I can imagine because it comes from peers at the highest level of scholarship in our nation,” Cella said. “I hope that my election might inspire others who work in outcomes research and health care improvement to strive to further their career goals and make an impact on our nation’s health.”

Cella also was the first scientist to explore the use of item response theory in health measurement, which helped generate new possibilities for better determining a patients’ symptoms, functioning and perceptions of overall health and well-being.

“Getting this high recognition from my peers reassures me that the work I do has value that matters to the people that matter: our patients,” Cella said. “Going forward, I will continue to search for ways to promote better health and encourage others to take on the challenges we face in delivering truly patient-centered health care and outcomes research.”

Susan Quaggin

Quaggin is the director of the Feinberg Cardiovascular and Renal Research Institute and chief of Nephrology and Hypertension in the Department of Medicine.

Susan Quaggin

Quaggin first joined the medical school in 2013 and since has led efforts in closing the gap between scientific discovery and delivering innovative patient care in regards to kidney and cardiovascular diseases. Her research has helped enhance the understanding of common glomerular diseases and inspired the development of promising therapeutics, including discoveries regarding blood vessels, lymphatics and specialized hybrid circulations.

“It is an incredible honor to be elected, one that I did not expect,” Quaggin said. “It is recognition of the teamwork performed with many incredible colleagues, trainees and collaborators that I have had the privilege of working with and learning from over the course of my career.

Quaggin, also the Charles H. Mayo, MD, Professor, has authored and contributed to more than 150 publications in nephrology and vascular biology.

“The work in the lab has always been inspired by my patients and this recognition spurs me on to work harder and continue to spread the message to future physicians that there is no better career than one combining patient care and science,” Quaggin said.

John Rogers

Rogers is the Louis Simpson and Kimberly Querrey Professor of Materials Science and Engineering, Biomedical Engineering and Neurological Surgery in the McCormick School of Engineering and Feinberg School of Medicine.

John A. Rogers

Rogers was elected to the National Academy of Engineering in 2011 and to the National Academy of Science in 2015.

A materials scientist by training, Rogers is an innovator in bio-integrated electronic devices, joining Northwestern University in 2016 to lead the Center for Bio-Integrated Electronics at the Simpson Querrey Institute. His research expands the capabilities of current biomedical technologies through creating innovative electronic devices that can be integrated with the human body and possess a wide range of diagnostic and therapeutic functions.

“At a personal level, I’m deeply honored to be selected to join this elite group but, more significantly, this recognition represents an important validation of our collaborative, interdisciplinary style of work at the interface between medicine and engineering science,” Rogers said. “As someone whose core training is in the physical sciences, I’m delighted to receive this form of endorsement, from the highest levels of the medical community.”

Rogers has published more than 530 papers and is an inventor with more than 80 patents and patent applications. He has founded several companies based on his research. His research uses new, innovative approaches to problems with the potential to change the fields of industrial, consumer and biocompatible electronics.

“We believe that the future of medicine will depend critically on advanced engineering and innovative technology concepts,” Rogers said. “We’re in a great position here at Northwestern — the right people, the right collaborative culture and the right resources and support — to help define that future.”

Catherine Woolley

Woolley is the William Deering Chair in Biological Sciences in the Weinberg College of Arts and Sciences and a professor of neurology in the Feinberg School of Medicine.

Catherine Woolley

Woolley has devoted her career to understanding estrogen actions in cognitive areas of the brain and sex differences in molecular mechanisms of synaptic plasticity. A neuroscientist by training, Woolley has authored and contributed to more than 75 publications over the course of her career.

“This is a great honor. I’m looking forward to engaging with members of the NAM and contributing my knowledge and expertise to the translation of basic discoveries in neuroscience to new medicines, therapies and policies to improve human health,” Woolley said.

Almost 30 years ago, as a graduate student, she discovered that estrogens drive synaptic plasticity in the hippocampus. Since then, her work has helped to explain how estrogens enhance learning and memory consolidation, and most recently her group has discovered new estrogen-based targets for anti-epilepsy therapies. Her research has also helped to develop a deeper understanding of Alzheimer’s, among many neurological diseases.

“Beyond my specific expertise as a scientist, I am also very interested in the NAM’s work on health policy and health equity,” Woolley said. “I grew up in rural southeastern Ohio, in the foothills of the Appalachian Mountains — the area I come from is one of the most beautiful places I know and also at risk from a hollowing out of the local economy and the hardships that result from this. I hope to use my experiences and connections to the area to help address the health needs of Appalachian communities, particularly related to addiction and mental health.”

Original story by Melissa Rohman appeared in Northwestern Now on 10/21/19.

Susan Quaggin, MD, is a member of the Chemistry of Life Processes Institute.

CLP startup MicroMGx Announces Collaboration with Corteva on Microbial-Based Crop Protection Products

CLP startup MicroMGx Announces Collaboration with Corteva on Microbial-Based Crop Protection Products

INDIANAPOLIS, Ind., Oct. 8, 2019 — Corteva Agriscience and MicroMGx today announced a collaboration that aims to provide farmers a wider range of novel, microbial-based crop protection products.

Under the agreement, MicroMGx will apply its metabologenomics platform to accelerate the identification of new natural product starting points.  In a first for the agriculture industry, Corteva will use those starting points to discover and develop naturally derived crop protection solutions.  Metabologenomics modernizes natural product discovery by fusing genomics and mass-spectrometry data in a way that facilitates more targeted molecule identification.

Farmers worldwide already rely on products developed by Corteva using spinosyns, active ingredients produced by naturally fermenting soil bacteria, to protect crops from insect damage.  The newest of these is Inatreq™ active, a new active ingredient that helps control fungus in wheat and bananas.

“With 20-plus years of leadership in green chemistry, Corteva Agriscience has a long and successful track record of discovering natural and naturally derived products,” said Neal Gutterson, Senior Vice President and Chief Technology Officer, Corteva Agriscience. “We are excited to collaborate with MicroMGx to explore novel approaches for speeding up the process of discovering the next generation of innovative crop protection solutions.”

“We believe in our platform’s potential to uncover impactful new crop-protection products. We’re enthusiastic to be partnering with Corteva Agriscience because of their strong portfolio of natural and naturally derived products,” said Anthony Goering, Chief Scientific Officer of MicroMGx.

MicroMGx part of a Midwest collaboration to bring exciting new technology to the world’s crop protection industry. Its metabologenomics platform was developed through a collaboration between research groups at Northwestern University’s Chemistry of Life Processes Institute and the University of Illinois’ Institute for Genomic Biology.

About MicroMGx, Inc.

MicroMGx, established in 2015, is a life sciences company dedicated to making high-throughput natural product discovery achievable. Through MicroMGx, pharmaceutical, animal health, and agriculture companies will have easy access to new natural products to fill their discovery pipelines. The MicroMGx laboratory is located at the University Technology Park at the Illinois Institute of Technology. Visit www.micromgx.com to learn more.

About Corteva Agriscience 

Corteva Agriscience is a publicly traded, global pure-play agriculture company that provides farmers around the world with the most complete portfolio in the industry – including a balanced and diverse mix of seed, crop protection and digital solutions focused on maximizing productivity to enhance yield and profitability. With some of the most recognized brands in agriculture and an industry-leading product and technology pipeline well positioned to drive growth, the company is committed to working with stakeholders throughout the food system as it fulfills its promise to enrich the lives of those who produce and those who consume, ensuring progress for generations to come. Corteva Agriscience became an independent public company on June 1, 2019, and was previously the Agriculture Division of DowDuPont. More information can be found at www.corteva.com.

Follow Corteva Agriscience on FacebookInstagramLinkedInTwitter and YouTube.

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Original press release issued on October 8, 2019 by Corteva Agriscience

MicroMGx cofounder Neil Kelleher is a faculty member of the Chemistry of Life Processes Institute.

The Best Laid Plans of Mice and Medicine

The Best Laid Plans of Mice and Medicine

“My plan was to become a pharmacist,” says Irawati (Angki) Kandela, PhD, Assistant Director of the Developmental Therapeutics Core (DTC), a CLP-affiliated core facility, and Research Assistant Professor in the Pharmacology Department at Northwestern.  Growing up in Indonesia where most of her family members were doctors, Kandela thought she would branch out into pharmacy.  Her goal was to someday rent space inside a family-owned clinic and handle patient prescriptions.  During her fourth year in pharmacy school, however, a new calling emerged.

“One night, I worked from seven until midnight adding non-active ingredients to increase the solubility of indomethacin and I really got into it,” says Kandela. “I realized then that research is fun and I should continue with it.”

Upon her father’s advice, she travelled to San Francisco in 1999 to learn English and apply for graduate school.  Six months later, she was accepted into the pharmaceutical sciences program at the University of Wisconsin-Madison.  Finding a way to pay for school was her next challenge.  Leveraging her pharmaceutical background, Kandela succeeded in securing a teaching assistant position that enabled her to graduate debt-free.

With her newly minted PhD, she accepted a position with radiopharmaceutical company Novelos, Inc. (formerly Cellectar) based in Madison, Wisconsin. Her research focused on targeted drug delivery using alkyl-phospholipid bound to radio-iodine 131 (I-131) for cancer treatment. After filing several patents, she was promoted to manager of the Biology Department.

“The job taught me a lot about GLP [good laboratory practice], IND [investigational new drug] applications to the FDA [US Food and Drug Administration], quality assurance, clinical teams, and making drugs for human beings,” says Kandela.

In 2011, she joined Northwestern University as a research associate with the primary responsibility of launching the Developmental Therapeutics Core facility within the Center for Developmental Therapeutics. Since then, more than 45 faculty members from across the University have tapped the core for its expertise in preclinical evaluation of new therapeutics, laboratory facilities and access to small animal models.  Kandela was promoted to research assistant professor in the Center for Developmental Therapeutics with a secondary appointment in the department of Pharmacology in 2017.

“We work with our hands, our energy and our minds,” says Kandela.  “On a typical day, I take care of all the studies in the morning to make sure the animals are checked, treated, or dosed. Afternoons are for clients and other business.”

From using models of patient-derived xenografts (PDX models) for a new cancer drug test, to evaluating the effectiveness of tiny, implanted neuro sensors, Kandela works with biologists, chemists and engineers on a variety of interesting projects. What keeps clients coming back is her work ethic, high standards, problem-solving, and positive attitude.  When initial study results disappoint, Kandela will suggest a modification, such as changing the frequency or concentration of the dose, combining the drug with another second drug, or repurposing another drug. These small tweaks often help projects get back on track.

“At the end of the day, we have to let the science guide us. You can’t rush things and you must stay open-minded.”

Her motivation runs deep.

“When my grandma died of brain cancer, I made a promise to be involved in drug development so that, hopefully, one day, a new drug would be on the market and I would play a tiny part in moving that process forward. To be able to make an impact like that would be wonderful.”

And what would she have told her ten-year-old self based on what she knows now?

“Just enjoy the ride,” says Kandela.

by Lisa La Vallee

Catching evolution in the act

Catching evolution in the act

Charles Darwin was right.

In his 1859 book, “On the Origin of Species,” the famed scientist hypothesized that artificial selection (or domestication) and natural selection work in the same ways.

Now an international team, led by Northwestern University, has produced some of the first evidence that Darwin’s speculation was correct.

This time, the study’s subjects are not exotic birds in the Galapagos, but instead a roundworm, which relies on its sense of smell to assess the availability of food and nearby competition. In the Northwestern-led work, researchers found that natural selection acts on the same genes that control wild roundworms’ sense of smell as were previously found in domesticated worms in the lab.

Erik Anderson Profile Picture

Erik Andersen, Associate Professor of Molecular Biosciences and CLP Member

“The evolution of traits is rarely connected to exact genes and processes,” said Northwestern’s Erik Andersen, who led the study. “We offer a clear example of how evolution works.”

The scientists used a combination of laboratory experiments, computational genomic analysis and field work. Their research also shows that natural selection acts on signal-sensing receptors rather than the downstream parts of the genetic process.

The study published this week (Sept. 23) in the journal Nature Ecology & Evolution. Andersen is an associate professor of molecular biosciences in Northwestern’s Weinberg College of Arts and Sciences.

A keystone model organism, C. elegans is a one-millimeter-long roundworm that lives in decaying organic matter — particularly rotten fruits — and feeds on bacteria. These roundworms are typically found in gardens and compost piles.

For C. elegans, having a keen sense of smell can be the difference between life or death. If they smell enough food in their environment, then they will stay, grow and reproduce. If they sense a shortage of food and/or too much competition from other worms, then they will undertake a long and potentially fatal journey in search of a more favorable environment. This process, called “dauer,” delays growth and reproduction.

In other words, dauer decreases reproductive success in the short term in order to ensure survival in the long run.

“At some point in their lives, these worms must make a gamble,” Andersen said. “In the time it takes for a worm to come out of dauer and start growing again, the worm that stayed behind has already been multiplying. If the food runs out, then the dauer worm  made the right decision and wins. If the food doesn’t run out, then the dauer worm loses.”

Andersen and his collaborators found that evolution plays a significant role in a worm’s decision to stay or enter dauer. Some roundworms have one genetic receptor to process scents; other roundworms have two. The roundworms with two receptors have a heightened sense of smell, which allows them to better assess the availability of resources in their environment and make a better gamble.

“If worms can smell large numbers of worms around them, that gives them an advantage,” Andersen said. “This was discovered in a previous study of artificial selection in worms. Now we also found that result in natural populations. We can see specific evidence in these two genes that artificial and natural selection act similarly.”

The study, “Selection and gene flow shape niche-associated variation in pheromone response,” was supported by a National Science Foundation CAREER Award. Daehan Lee, a postdoctoral researcher in Andersen’s laboratory, was the paper’s first author.

Original story published in Northwestern Now on 9/26/19 by Amanda Morris.

Erik Andersen is a member of the Chemistry of Life Processes Institute.

Learn more about his work.

 

Viewing Party to Celebrate National Chemistry Week

Viewing Party to Celebrate National Chemistry Week

In celebration of National Chemistry Week, Chemistry of Life Processes Institute (CLP) and Northwestern’s Undergraduate Chemistry Council will host a free viewing party of American Chemical Society’s ‘Program in-a-Box Marvelous Metals’ on Tuesday, October 22, 2019, 5:30 – 7:00 p.m. CST. The live, interactive online program will include a guest appearance and Q&A by CLP member Thomas J. Meade, PhD (Chemistry, Molecular Biosciences, Neurobiology, and Biomedical Engineering).

Thomas J. Meade, PhD (Chemistry, Molecular Biosciences, Neurobiology, and Biomedical Engineering

Thousands of students and early career chemists from around the world are expected to join to learn how chemists are developing new technologies using metals at the intersection of organic and inorganic chemistry. From innovations in medical imaging and theranostics to fundamental changes to the way we create everyday necessities like clothing, food, and energy, Meade and Vy M. Dong, PhD, Full Professor of Natural Sciences, University of California, Irvine, will demonstrate how we can harness the power of our “marvelous metals.” What to Expect

  • A live interactive video broadcast featuring presentations and Q&A with experts in organometallic chemistry.
  • Professor Vy Maria Dong will discuss the importance of organic chemistry processes to the industries that power modern society and how she is using metals to create improved reagents, catalysts, and strategies for a more sustainable and greener future.
  • Professor Thomas J. Meade will define molecular imaging, what it can currently do in the clinic, and how his “bioactivated” or “conditionally activated” probes could revolutionize how we diagnose and even treat patients during the diagnostic phase.
  • The first to answer “Marvelous Metal Trivia” on Twitter with #ACSPIB will get a shout out live on-air!
  • Opportunity to meet thousands of fellow students and professionals around the world on Facebook, Twitter, and Instagram by posting with the event hashtag #ACSPIB.
  • Raffle prizes, handouts, and other ACS resources.
  • Free pizza, snacks, treats and beverages!

Space for the viewing party is limited. Admission is on a first-come, first-served basis.

Can’t make it to the party? Watch the program from the comfort of your own home or dorm community room. Follow #ACSPIB on Twitter and Instagram and go to www.acs.org/pib to check-in as an individual to watch the live broadcast beginning at 5:45pm CST on October 22nd, 2019.

Please contact Lisa La Vallee, lisa.lavallee@northwestern.edu, if you have any questions, or wish to learn more.

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Dissolvable Optical Sensor Moves Medicine Forward

Dissolvable Optical Sensor Moves Medicine Forward

Treating severe brain injury often requires immediate surgery, including implantation of an electronic sensor that monitors tissues and fluids and digitally provides real-time information about intracranial pressure, temperature and wound healing.  These devices, however, have one major drawback: eventually, they must come out, requiring an additional surgery to extract the device from the body and concomitant risk and expense.

In a recent Nature Biomedical Engineering study, a team of Northwestern scientists led by John Rogers (materials science and engineering, biomedical engineering and neurological surgery) introduces a new type of sensor, one that completely dissolves in the body when no longer needed. The study also successfully deploys a powerful, new photonics-based optical technology developed by lead author Wubin Bai, a postdoctoral fellow in John Rogers’ lab.

“This is the first time we’ve brought the ideas of biodegradable technologies into the realm of optics and photonic systems” says Rogers. “Optical characterization of tissue can yield quantitative information on blood oxygenation levels. Fluorescence signals can reveal the presence of bacteria as a diagnostic for the formation of an infection at an internal wound site. Fluorescence-based calcium imaging can reveal metrics of brain activity. There are also ways that light can be used to activate certain biological processes and that’s a next step for us.”

The work fits into a broader context of Rogers’ lab that develops materials for electronic, semiconductor or optical systems designed to go into the body, perform diagnostic and therapeutic functions, then dissolve after a pre-determined amount of time.  In addition to providing critical information about physiological function, implantable sensors also can function as electrical stimulators for accelerating the rates of neural regeneration in damaged peripheral nerves, or as drug delivery agents electronically programmed to release drugs at certain time points.

From clinical needs to breakthrough solutions  

“The project started with an idea that came from a discussion with professors in the clinic,” says Bai.

From skin patches worn by Gatorade-sponsored athletes to monitor rehydration needs to wireless monitors that track the vital signs of premature babies, Rogers’ team regularly collaborates with doctors and surgeons across the country to develop innovate solutions to thorny problems that arise in the clinic. He estimates that his lab has more than 20 active Institutional Review Board-approved studies of other technologies involving human subjects underway at Northwestern alone.

Rogers’ lab is looking to expand the biodegradable electronic technology to heart applications for both adults and children, in response to inquiries from Northwestern cardiologists. The doctors identified a need for a programmable sensor to monitor the oxygen level around the heart during surgery with children.  They also sought solutions for a temporary pacemaker to deliver electrical stimulation, as necessary, during a recovery period following a heart surgery. After a specific time has elapsed, the devices naturally dissolve away and disappear in the body.

“One of the biggest challenges was integrating heterogeneous biomaterials together to form a functional and bioresorbable system making all of the constituents of the materials of the devices bioresorbable,” said Bai. “We had to precisely control both the composition materials’ chemistry and the device design, and dosage of each parameters together.”

Using substances naturally found in the body, the team created coating layers that dissolved very slowly. Inside, they used primarily silicon and zinc to create the functional materials for photodetection and electrical readout. The researchers then fabricated and tested three different devices useful for specific applications, all micron scale and smaller than the tip of a needle in final form. The first was composed of a silicon nanomembrane designed to detect a light at a single wavelength to monitor changes in blood flow. The second incorporated three such devices in a stack to detect multiple colors, as a simple form of chemical spectroscopy.  The third contained an optical filter allowing for precise control for sensing neuron activity.

Bioresorbable, silicon-based mechanical/physical/chemical sensors for biomedical applications

Designing the experiments

Integral to the biological aspects of the research were five experts from Chemistry of Life Processes Institute-affiliated core facilities and coauthors of the study who worked closely with Bai to plan and implement the study’s extensive in vivo proof-of-concept experiments.

Fraser Aird, PhD, and Irawati Kandela, PhD, and Iwona Stepien with the Developmental Therapeutics Core, conducted in vivo experiments to check for any immune responses in the blood to the device.  The lack of immune response meant the device was not toxic to the mice. Jessica Hornick, PhD, Biological Imaging Facility, measured immune response and tissue regrowth after implantation at various timescales. Her findings concluded tissue bounced back and the device wasn’t toxic to the body. Chad Haney, PhD, and Anlil Brikha with the Center for Advanced Molecular Imaging, performed the CT imaging. CAMI’s images provided powerful physical evidence that the device disappeared slowly from week to week until it fully reabsorbed into the body. The final test was to determine whether traces of the device remained in the organs. Keith MacRenaris, PhD, Quantitative Bioelement Imaging Center, analyzed the organs throughout the experiment to measure the different concentrations of zinc and silicon, the materials used to make the device, and found these too dissipated over time.

“The core facilities have been a fantastic resource for us,” says Rogers. “Sometimes you’re working in an out-of-the-box area and it’s very much exploratory and it can be non-trivial to find collaborators with the necessary animal expertise. As a result, there can be an activation barrier for people engaged and involved.  Having the cores as an additional option for collaborator-based research around the biological aspects is great thing.”

by Lisa La Vallee

Feature image: Wubin Bai, Professor John Rogers, and Jessica Hornick huddle in the Biological Imaging Facility, a CLP-affiliated core facility that collaborated on the study.