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Chemistry Undergraduate Charlie Wang Awarded 2020 CLP Lambert Fellowship

Charles Tiancheng Wang, a third-year Chemistry student at Northwestern, was awarded the 2020 Lambert Fellowship, the Chemistry of Life Processes Institute’s (CLP) most prestigious undergraduate award. The Fellowship was endowed in 2016 by Andrew Chan, MD, PhD...

Medical device using Northwestern-invented biomaterial receives FDA clearance

Medical device using Northwestern-invented biomaterial receives FDA clearance

An innovative orthopedic medical device fabricated from a novel biomaterial pioneered in the laboratory of Northwestern University professor Guillermo A. Ameer has received clearance from the U.S. Food and Drug Administration (FDA) for use in surgeries to attach soft tissue grafts to bone.

The biomaterial is the first thermoset biodegradable synthetic polymer ever approved for use in an implantable medical device. It’s unique chemical and mechanical properties enable cutting-edge implant designs that protect the soft tissue graft during insertion and optimize graft fixation to bone.

ameer citregen

CLP Member Guillermo A. Ameer

Ameer’s biomaterial, called CITREGEN™, helps grafted tissues heal by recreating their intrinsic biochemical and structural support network.

CITREGEN’s critical component, citrate, is a naturally occurring anti-microbial and anti-inflammatory molecule that plays a crucial role in boneregeneration, where it regulates cellular metabolic processes and the formation of mineral structures. Ameer spent more than 15 years studying citrate to develop new materials for regenerative engineering. This work that has been expanded upon by other researchers around the world, most notably Jian Yang, Ameer’s former postdoctoral trainee and current chair of The Lloyd and Dorothy Foehr Huck Center for Regenerative Engineering at The Pennsylvania State University.

“CITREGEN is an unprecedented and innovative bioresorbable biomaterial technology developed to support the body’s normal healing process and promote tissue regeneration,” Ameer said. “When used to fabricate devices for reconstruction of tissues, such as ligaments, blood vessels, bladder and bone, results have been impressive and beyond our expectations.”

Ameer is the Daniel Hale Williams Professor of Biomedical Engineering in Northwestern’s McCormick School of Engineering and a professor of surgery in Northwestern’s Feinberg School of Medicine. He also is founding director of Northwestern’s Center for Advanced Regenerative Engineering.

1Ameer’s biomaterial is the first of its kind approved for use in an implantable medical device

CITREGEN is the core material technology in the CITRELOCK™ Interference Screw System, which will be produced and marketed by Acuitive Technologies, Inc. The system is intended for soft tissue attachment or fixing ligaments and tendon graft tissue in joint surgeries. After surgery, CITREGEN releases molecules essential to bone formation. As CITREGEN is absorbed by the body, it leaves behind a biocompatible ceramic structure that is metabolized by the body’s tissue. This bioresorption process avoids the bulk degradation and chronic inflammation that commonly accompanies other biodegradable polymers on the market.

The CITRELOCK Interference Screw System will become available through Acuitive’s orthopaedic distribution partner in early 2021.

“After almost two decades of research on this advanced materials technology, I am delighted to see a transformative product get FDA clearance and come to market, an effort led by a spectacular team at Acuitive,” Ameer said.

Ameer also is a member of the Simpson Querrey Institute, Chemistry of Life Processes Institute and International Institute for Nanotechnology.

Editor’s note: Acuitive Technologies is a sublicensee of Ameer’s company Vesseltek Biomedical. Northwestern and Ameer have financial interests in Vesseltek Biomedical.

Main image: CITRELOCK tendon fixation devices. Credit: Acuitive Technologies

Northwestern’s Thomas Meade Awarded World Molecular Imaging Society Gold Medal Award

Northwestern’s Thomas Meade Awarded World Molecular Imaging Society Gold Medal Award

Thomas J. Meade, the Eileen M. Foell Professor of Cancer Research and Professor of Chemistry, and member of the Chemistry of Life Processes Institute (CLP) at Northwestern University, was awarded the World Molecular Imaging Society’s highest honor. The 2020 Gold Medal Award recognizes Meade’s “pioneering work in the fields of magnetic resonance and optical molecular imaging, providing solutions for deep tissue imaging and for advancing quantitative and biologically specific interrogation of living systems.” Meade, Professor of Chemistry, Molecular Biosciences, Neurobiology, Biomedical Engineering and Radiology, will receive the award during the World Molecular Imaging Congress (WMIC Virtual 2020), October 7-9, 2020.

Meade is widely recognized for his pioneering work in the field of conditionally activated magnetic resonance (MR) agents and the development of probes for MRI and optical imaging.  In collaboration with the CLP, Professor Meade designed the Center for Advanced Molecular Imaging to perform transdisciplinary research from molecule to whole animal. He is the former President of the Society of Molecular Imaging and founder of Imaging in 2020, a biannual conference focusing on all aspects of imaging.

Meade received his master’s in Biochemistry and PhD in inorganic chemistry. After completing a NIH fellowship in Radiology at Harvard Medical School, he was a postdoctoral fellow at the California Institute of Technology. In 1991, he joined the Division of Biology and the Beckman Institute at Caltech. In 2002 he moved to Northwestern University, where he is the Director of the Center for Advanced Molecular Imaging (CAMI).

Professor Meade’s research focuses on coordination chemistry and its application in bioinorganic problems that include biological molecular imaging, electron transfer processes and the development of electronic biosensors for the detection of DNA and proteins. He has received numerous awards and in 2009 was a Miller Professor at the University of California Berkeley. He holds more than 100 US patents and has founded five biotech companies, Clinical Micro Sensors, Meataprobe, PreDx, Ohmx and DetEctz, which are developing hand-held detection devices for protein and DNA detection and bioactivated MR contrast agents for clinical imaging.

by Lisa La Vallee

 

 

CLP Welcomes 2020/2021 NIH Graduate Program Trainees

CLP Welcomes 2020/2021 NIH Graduate Program Trainees

This fall, the prestigious NIH-funded Chemistry of Life Processes Training Program welcomed five second-year predoctoral students and three third-year trainees whose appointments were renewed. Trainees are required to have dual mentors from both chemistry and the life sciences and to learn the methods and approaches of both laboratories.  Throughout the two-year program, students engage in immersive, transdisciplinary laboratory training, and coursework in chemical biology methods and experimental design that will prepare them to tackle the world’s biggest problems in human health and disease.  They receive support investigating and developing the skills needed to pursue independent careers.  They learn about development of new drugs and diagnostics, entrepreneurship, and team science.

The program also gives students the tools and practice needed to become adept at communicating their science to a broad audience. Research forums and improv workshops give students hands-on experience communicating the impact of their research in the simplest and most compelling terms to audiences of varying levels of expertise.

“Former trainees who have since graduated and have full time jobs, have told us how important the program turned out to be for their career,” says Penelope Johnson, Senior Project Coordinator and program coordinator for the training program.  “In their companies, they are not always talking to scientific colleagues. If they need to defend an expense to a budget manager, for example, they need to make a persuasive case that does not involve a hypothesis and conclusion. What that budget manager wants is a two-minute, bottom-line answer to ‘Why should I keep investing money in this project?’”

CLP trainees get to invite visiting professors to Northwestern to give seminars and also learn from pharma and biotech experts on CLP’s Executive Advisory Board, as well as previous trainees who have graduated from the program and moved on to exciting careers in biomedical research.

“CLP trainees are constantly learning from each other and finding new solutions to challenges encountered in their research,” says Johnson.

Meet the cohort

The ‘20/’21 trainees have shared their responses to the questions: ‘Why did you apply to the training program and what you hope to get out of it?’ and ‘What do you look forward to the most?’

Newly appointed second year graduate students:

Ben Brenner
Primary Mentor: Hao Zhang
Secondary Mentor: Tom O’Halloran
Department: Biomedical Engineering

I applied to the CLP training program to achieve better specialization in Chemistry than might be possible in the standard training offered by the biomedical engineering department. I think it will open up many collaborative opportunities for my research.  I look forward to learning about the research of my fellow CLP members and of the researchers who speak at the seminars.

Alex Lee
Primary Mentor: Daniel Foltz
Secondary Mentor: Neil L Kelleher
Department: Biochemistry and Molecular Genetics

I applied to the CLP training program because I was interested in utilizing chemical approaches to study how deregulation in biological processes could lead to human disease. Apart from working on an independent research project with mentors that speak the languages of chemistry and biology, I hope to use this as a platform to foster diversity, scientific awareness, and collaboration within Northwestern University and the greater scientific community. What I look forward to the most is getting to know the CLP community, as well as connecting and learning from various guest speakers in academia and industry.

Cydney Martell
Primary Mentor: Gabriel Rocklin
Secondary Mentor: Mike Jewett
Department: Biological Sciences

I applied to the CLP training program for the opportunity to work with a secondary mentor and the focus on interdisciplinary research. Through this rotation, I hope to learn more lab techniques and different approaches to progress my thesis project. I also hope to continue to build my network and develop relationships that can foster collaboration in the future.

I most look forward to building relationships with the other trainees in my cohort. As a student on the Chicago campus, I am excited to build connections with graduate students and professors on the Evanston campus. I am looking forward to the research forums because of the ability to work on communicating my science and learn about my peer’s research. This will be a beneficial space to learn from the expertise of my peers and their suggestions for progressing my research.

Bethel Shekour
Primary Mentor: Milan Mrksich
Secondary Mentor: Karl Scheidt
Department: Chemistry

I applied to CLP because of the sense of community and support among cohort members. Not only do we get to grow as researchers together, but we also get the opportunity to discuss our research with those who are in different fields from ours. This helps us to grow as better communicators and enables us to share and receive new perspectives on how to address our research questions. I look forward to meeting everyone in-person and cheering them on as they accomplish amazing things.

Frank Tucci
Primary Mentor: Amy Rosenzweig
Secondary Mentor: Yuan He
Department: Interdisciplinary Biological Sciences

 I applied to CLP because I understand biology as a function of chemistry. I enjoy thinking about questions at the interface of these disciplines and looking at biology through the lens of chemistry. I am looking forward to interacting with my cohort and other scientists who are interested in chemical biology as well as learning about exciting research at the interface of chemistry and biology.

Renewed third-year postdoctoral students:

Israel Da Silva
Primary Mentor: Regan Thomson
Secondary Mentor: Neil L Kelleher
Department: Chemistry

I applied to CLP because it matched my scientific interests (chemistry and biology) and it also provided a lot of support for my career and personal life which I found very valuable. I look forward to applying all the skills I have learned in graduate school and CLP workshops to see how far in my scientific career I can get.

Allison Devitt

Primary Mentor: Karl Scheidt
Secondary Mentor: Peter Penzes
Department: Chemistry

I applied to the training program because I wanted the funding and support to move my very early stage project into a more applied direction. I hoped to find direction for my project and get training and advice to allow me to be a better, more well-rounded researcher. What I look forward to the most is seeing my cohort and Penelope [Johnson], the light of every CLP event.

Tori Seto
Primary Mentor: Milan Mrksich
Secondary Mentor: Alex Stegh
Department: Chemistry

I applied because the CLP program’s goal to train scientists in chemistry and biology aligned well with my own research and career goals to become an interdisciplinary scientist.  I look forward to CLP events and seminars because they always provide a great networking opportunity and learning experience.

“It’s rewarding to see the progress that students make over the course of the year,” says Johnson. “With practice and persistence, they realize being curious and asking questions can open up new collaborations and working relationships.

“I am excited about this year’s cohort building their professional network, practicing their science communication and learning from each other. The power of the cohort is enormous!”

by Lisa La Vallee

 

13-mile “Northwestern-to-Northwestern” Lake Michigan Swim to Benefit ALS Research

13-mile “Northwestern-to-Northwestern” Lake Michigan Swim to Benefit ALS Research

Barrington resident Doug McConnell is one of the few people in the world who have swum the English Channel and also conquered Hawaii’s Ka’iwi Channel, Catalina Channel, and Tampa Bay.  His inspiration was a passion for raising awareness and funds for ALS, also known as Lou Gehrig’s disease. McConnell lost his father, Dave, to the disease in 2006, and recently his sister Ellen, in 2018. A competitive swimmer for more than 50 years, McConnell co-founded A Long Swim to raise money for ALS research by completing marathon-distance swims.

This year, McConnell will embark on a 13-mile “Northwestern-to-Northwestern” Lake Michigan swim to raise funding for collaborative ALS research directed by Hande Ozdinler, PhD, Associate Professor of Neurology at Northwestern University Feinberg School of Medicine.  Ozdinler is a member of the University’s Chemistry of Life Processes Institute  (CLP) here team scientists from across disciplines engage to find new cures for ALS and other diseases.

Hande Ozdinler profile picture

Hande Ozdinler, PhD, Associate Professor of Neurology at Northwestern University

“I am honored to have the support of A Long Swim and to have the opportunity to initiate and foster new collaborations,” says Ozdinler.  “Team-based science is the only way to defeat ALS. Our lab has made tremendous progress in understanding why motor neurons die in ALS and other motor neuron diseases, such as HSP and PLS, and through our affiliation with the Chemistry of Life Processes Institute. The discoveries will also have implications in HSP, PLS, and other motor neuron diseases. I look forward to making even greater strides to identify novel drugs and biomarkers for neurodegenerative diseases.”

McConnell will begin his fundraising swim at Northwestern’s Evanston campus and finish at the Feinberg School of Medicine near Navy Pier in Chicago.

“We began funding the efforts of Hande nine years ago, since then her lab has pioneered the study of upper motor neurons and identified the mechanisms behind neurodegenerative diseases,” says McConnell. “When it comes to ALS, Hande is a fearless and brilliant champion. We’re very lucky to have her in our corner.”

The Ozdinler Lab has established several collaborations with CLP faculty members. Together with Richard B. Silverman, PhD, the inventor of Lyrica, the team is developing compounds that could have an effect on degenerating upper motor neurons. Last year, the project received a $3.1 million drug discovery grant from the National Institutes of Health. Collaborations with Neil Kelleher, PhD, and Shad Thaxton, PhD, have led, respectively, to new discoveries for ALS biomarkers and the investigation of the mode of disease transmission via exosomes.

“CLP is home to many great and collaborative scientists who are willing to work and discover together. This is how we will move the field forward,” says Dr. Ozdinler.

In addition to completing the English Channel swim, McConnell and his team have completed five other swims considered “marathons” with distances ranging from 15-32 miles and has raised more than $1 million in support of ALS since 2011.

McConnell’s quest didn’t end there. He is continuing the mission of A Long Swim, “To use marathon-distance swimming to raise funds for collaborative ALS research.”  With the net proceeds of A Long Swim’s activities, it specifically funds the Ellen McConnell Blakeman Research Fellowship in the Ozdinler Lab, which is named after McConnell’s sister. The recipient of the Fellowship, Dr. Mukesh Gautam, has also received international recognition for his scientific work.

ALS is a disorder that disrupts the ability of nerves to transmit signals to the muscles.  As a result, muscle groups degrade to the point where digesting food and even breathing are impossible. Based on U.S. population studies, a little over 6,000 people in the U.S. are diagnosed with ALS each year. (That means that someone is diagnosed with ALS every 90 minutes.  Sadly, someone also dies from ALS every 90 minutes.) It is estimated that as many as 30,000 Americans have the disease at any given time. A Long Swim was formed as the perfect contrast to the effects of disease; while an ALS patient gradually loses the use of their muscles, swimming requires us to use all of our muscles, all the time.

A Long Swim continues to host open water swims, and tackle challenges in several open water adventures raising money for ALS. McConnell and his team of volunteers research, plan and execute swims across the globe and maneuver wildlife including jellyfish and sharks. They pledge to continue to host events and participate in fundraisers until patients become ALS survivors.

Donations can be made at ALongSwim.com/northwestern-to-northwestern or on CrowdRise. Please visit www.ALongSwim.org for additional information.

Join the Zoom Launch Party!

On September 9 at 7:00 p.m. CST A Long Swim will host a Zoom Launch Party for the Northwestern to Northwestern Swim.  To join, click here and enter the meeting ID: 998 5329 6108 and Passcode: 240477.

About Chemistry of Life Processes Institute

Chemistry of Life Processes Institute at Northwestern University is where new cures and biomedical discoveries begin.  The Institute’s 65 faculty represent more than 20 University departments that span the schools of arts and sciences, engineering and medicine.  CLP provides comprehensive support for high-impact team science through four research centers of excellence, seed grants for collaborative science, expert project support, and eight world-class research resources for innovation and translation.

CLP accelerates innovation and translation at Northwestern. Since its founding, the Institute has advanced more than 75 new drug candidates, medical devices and diagnostic tools towards clinical trials.  CLP investigators have spun out 27 new companies that have attracted more than $2 billion in investment. The Institute’s rigorous training programs prepares future scientists to work across disciplines to lead next generation science, medicine, and technology breakthroughs.

clp.northwestern.edu

Andy Chan Receives 2020 Northwestern Alumni Medal

Andy Chan Receives 2020 Northwestern Alumni Medal

Northwestern’s Alumni Association announced today that Andrew Chan, Senior Vice President of Research Biology, Genentech, and Chair of Northwestern’s Chemistry of Life Processes Institute (CLP), will receive the 2020 Northwestern Alumni Medal. He was one of four distinguished alumni to receive the NAA’s highest honor for the positive impact they have made in their careers and communities.

“I am delighted that Andy has received one of the most prestigious awards bestowed on Northwestern alumni. It is well earned!” says Tom O’Halloran, the Charles E. and Emma H. Morrison Professor of Chemistry and Professor of Molecular Biosciences in the Weinberg College of Arts & Sciences, and Founding Director of CLP. “As one of the first members of the CLP Executive Advisory Board  and now as Chair of the Board, he continues to bring a generous spirit and a deep knowledge of science and drug discovery into the service of Northwestern.”

Chan began serving on CLP’s Executive Advisory Board in 2007 and became chair in 2015.   His contributions to the research and training mission of the Institute and Northwestern are many.  Under Chan’s leadership, the CLP Board has deepened its engagement and funding for bold new research and translation programs, such as the CLP-Cornew Innovation Fund and initiatives, and the CLP-Oppenheimer Investor Conference that help bring faculty discoveries and new treatments for disease to society.

Andy Chan (top row, second to the left) founded the CLP Lambert Fellows Program in 2010 and endowed it in 2016 in honor of Joseph Lambert.

The Lambert Fellows Program, which was endowed through Chan’s generosity, has made an indelible mark on the lives of many Northwestern undergraduates. Their post-graduate successes reflect the impact of their training in CLP labs.  In addition, Chan has served as a valuable mentor to graduate students in the CLP Training Program and an enthusiastic participant in the Institute’s career development activities.

“Andy understands the motivations, challenges and hurdles of professors and their trainees who are trying to uncover the fundamental chemistry of living systems in general and disease processes more specifically,” says O’Halloran. “We are so grateful for the wisdom he has freely shared with Northwestern faculty, staff, and graduate and undergraduate students, as we work towards translating academic discoveries into new medicines.”

Andrew Chan is senior vice president of research–biology at Genentech, a biotechnology company that works to develop medicines for people with serious and life-threatening diseases.

An accomplished immunologist and drug developer, Chan leads more than 1,100 scientists in biological research spanning therapeutic areas of oncology, immunology, neuroscience, infectious diseases, and protein sciences. His research is focused on understanding how changes in the immune system may result in disease. He is the coinventor of ocrelizumab, an antibody approved by the U.S. Food and Drug Administration for the treatment of multiple sclerosis.

Through his leadership roles on several committees, Chan oversees Genentech’s research programs and priorities, and early clinical development portfolio. He also helps shape the company culture as a member of the Genentech Research and Early Development Leadership Team.

Before joining Genentech in 2001, Chan was a faculty member in the departments of medicine and pathology at the Washington University School of Medicine in St. Louis, and served as an investigator for the Howard Hughes Medical Institute. He completed his internal medicine residency at Barnes Hospital in St. Louis, and rheumatology fellowship at University of California—San Francisco (UCSF).

Chan sits on the National Council of the Washington University School of Medicine, the scientific advisory board of the Arthritis Foundation, and the Rosalind Russell/Ephraim Engleman UCSF Arthritis Center.

Chan holds a BA and MS in chemistry from Northwestern, and an MD and PhD in cellular and developmental biology from Washington University School of Medicine. He and his wife, Mary, have two children, Michael and Jennifer.

by Lisa La Vallee

 

 

 

Improv helps Northwestern graduate students build a better science pitch

Improv helps Northwestern graduate students build a better science pitch

“When scientists, or anyone in a STEM field, are communicating their work, it needs to have a ‘so what’ factor. Why does this matter to me, or why should I care about what it is that you’re telling me,” says Heather Barnes, Founder of Improv @ Work, LLC, and  a faculty member of The Second City, home to Chicago’s renowned improvisational comedy center.  “I find again and again, scientists don’t start with that. They start with the details and immediately disengage their audience. The main point is lost, as is the opportunity [for the listener] to engage in the scientific process and to teach someone something.”

Earlier this year, Northwestern University’s Chemistry of Life Processes Institute (CLP) invited Barnes to lead a full-day improv-based science communications workshop for graduate students in its NIH Postdoctoral Training Program.  The program trains highly qualified graduate students in chemistry, biology and engineering to work across disciplines and apply cross-disciplinary approaches and tools to their research. It also provides exclusive opportunities to interact with academic and industry leaders and develop valuable career skills.

“Our graduate trainees are so smart and really excel at science,” said Penelope Johnson, Senior Project Coordinator and program coordinator for the NIH-funded CLP Predoctoral Training Program, “Because their knowledge is so advanced, it can be hard sometimes to communicate what they are doing in the lab to someone like me who doesn’t know anything about science.”

For more than 20 years, Barnes has helped researchers and scientists, from universities and medical centers to museums, make their work more accessible to key stakeholders. As Director of the Aquatic Presentation at the John G. Shedd Aquarium and, previously, at the Museum of Science and Industry, Barnes delighted audiences with innovative programs guided by the principles of improvisation.

Barnes teases out students’ insecurities by creating a safe space for experimentation, as well as failure.

“People are quick to judge themselves. There’s a big fear of I’m not a good public speaker, or this is not something I can do,” says Barnes.  “A big part of the work is how we process a mistake, move on and show our human side. We want to free up people’s judgment of themselves and of each other.”

According to a new study by researchers at the University of Michigan and Stony Brook University, after just 20 minutes of theater improv experience, people feel happier, more creative and tolerant of uncertainty. The key is learning how to relax, live in the moment, and talk with—not at—your audience. Barnes challenges students to distill their messages using audience input, instead of undeviating from a memorized, rigid script.

“It’s so important because if we aren’t able to get our message across to the public or to funders, then we’re not going to engage people or get funding. We’re not going to have people voting on our issues and our topics,” said Barnes.

Breaking down barriers

During the morning half of the workshop, Barnes introduced students to basic improv activities.

“We get up and immediately break down barriers by doing some things we may be terrified of doing in public like moving like a Britney Spears backup dancer while counting backwards from eight to one,” says Barnes. “By immediately creating a positive, supportive and fun environment for making mistakes together, we create a safe space for failure. A big part of the work is teaching people to get comfortable being uncomfortable. It’s important to free up judgment of ourselves and of each other. This allows everyone to see that we can succeed and get through even the toughest situations.”

The exercises paid off as the young scientists began to loosen up.

“At first, I was nervous—I’ve always gone to improv shows and thought I could never do improv and would be too scared to try,” says workshop participant Marija Milisavljevic. “But, it turns out, in a small setting with a great instructor and some awesome people, it’s so much fun.”

Distilling the message

In the afternoon, students practiced distilling their messages.  Barnes paired up students and asked them to take turns talking about their work in under three minutes. After receiving feedback from their partner, students would try their elevator pitch again until, eventually, they succeeded in boiling it down to one minute.

“It was pretty incredible how much students improved their pitches just by having someone else listen and offer advice on how to make their segment more relatable,” says Johnson.

Rather than just reciting talking points, Barnes encouraged students to use stories, make analogies, and offer emotional examples to pique and hold their audience’s interest. She also advised students to ask a question in the first 60 seconds of their talk to keep audience members actively engaged.

“I’ve always struggled with explaining what I do to my friends and family who aren’t in STEM fields,” says Milisavljevic. “So much of what we were doing wasn’t about us individually, but about the group as a whole. I loved this message because I think progress in science is all about groups collaborating and sharing and communicating ideas effectively for the greater good.”

To quell concerns about oversimplification or “dumbing down” their work, Barnes played a popular science video in which the speaker completely avoided the use of scientific terminology.

“Research bears out that if you’re able to talk in an accessible language and avoid jargon, people actually think you’re more intelligent than if you’re just talking over people’s heads using industry and role specific jargon. ” says Barnes.

The workshop struck a chord with participants.

“It was a breath of fresh air,” said Luifer Schachner, a sixth-year graduate student participant. “I came out invigorated, relaxed, and excited to keep working on my science.”

by Lisa La Vallee

The Protein Whisperer

The Protein Whisperer

As research laboratories on campuses across the US slowed down in March in response to stay-at-home orders, Northwestern’s Recombinant Protein Production Core (rPPC), a Chemistry of Life Processes Institute-affiliated core facility, was running at full speed.

In response to the urgent cry for new treatments and vaccines to slow the spread of the SARS CoV-2 virus, Sergii Pshenychnyi, Managing Director of the rPPC, flew into production mode. His number one customer—Northwestern’s Center for Structural Genomics of Infectious Diseases (CSGID)—required his services for purification of the virus’s proteins. The Center was acting upon a direct request from the National Institute of Allergy and Infectious Diseases (NIAID), led by Anthony Fauci, MD, for structural studies of SARSCo-V2 proteins.

“If there was ever a time to redirect your research towards a pathogen that, frankly, we as a civilization of the planet have never seen before— this was it,” says Michael Jewett, the Walter P. Murphy Professor of Chemical and Biological Engineering, Director of the Center for Synthetic Biology, and Co-Director of the rPPC.

An important first step in defeating any virus is mapping its protein structure. Proteins provide an entryway for the virus to invade the body by modifying its genetic material so it can hide from the immune system and safely multiply. Defining the 3-D structure of a virus allows drug developers to identify inhibitors that block their action or to search for drugs already approved by the FDA that could work against them.

SARS-CoV-2 is comprised of dozens of continually mutating proteins. Scientists need to understand and track the differences of not only the initial variants of the proteins, but also the mutated variants as well.

“We need lots of protein structure information to develop new therapies,” says Karla Satchell, a microbiologist in the Feinberg School of Medicine, and the head of CSGID, an international consortium of eight institutions funded by the National Institute of Health, that uses protein crystallization to investigate the structures of emerging infectious agents. “We reach out to Sergii for difficult proteins on a regular basis.”

Satchell enlisted Pshenychnyi to produce and purify two proteases central to the function of the virus that are considered likely candidates for drug targets: the SARS-CoV-2 papain-like protease (PLpro) and chymotrypsin-like protease (3CLpro).

“Usually projects like these take two weeks at minimum, but I did it in four days,” said Pshenychnyi who says the high-stakes project triggered a rush of adrenaline. “As soon I produced the protein, CSGID was there within 15 minutes to package it up and FedEx it to Purdue.”

Investigators at Purdue University, a key CSGID collaborating institution, then were able to process the protein material into crystals and use powerful x-rays to analyze the protein’s structure. In record time, they were able to inform the NIAID that none of the existing HIV treatments would be effective against SARS-CoV-2, but that certain Hepatitis C drugs looked promising. To date, the center is responsible for solving about one third of all SARS-CoV-2 protein structures globally.

“This was a major role,” says Satchell, “because these viral protease inhibitors for HIV and HCV were being used in the clinics without any evidence that they would work.”

“We need to have as many shots on goal as we can. Sergii is one of these people that can multitask and get many shots on goal very quickly,” says Jewett.  “He has put in tireless hours directing the research efforts of the rPPC to address this pandemic.”

Jewett likens Pshenychnyi’s skill to that of a famous chef running a five-star Michelin restaurant.

“Some people just technically have the secret sauce in their hands. Sergii is an excellent chef of essentially making these proteins,” says Jewett. “There is somewhat of an art form to it and Sergii has that.”

by Lisa La Vallee

Northwestern, Argonne, and partners to launch national resource to unlock the role of metals in human health

Northwestern, Argonne, and partners to launch national resource to unlock the role of metals in human health

Evanston, IL – June 26, 2020: Chemistry of Life Processes Institute (CLP) at Northwestern, the Advanced Photon Source (APS) at Argonne National Laboratory, and several leading research universities, will join forces to launch a first-ever national hub for interdisciplinary, metallomics research and innovation.

The National Institutes of Health (NIH) has awarded Northwestern a five-year, $8.2 million grant to establish the Resource for Quantitative Elemental Mapping for the Life Sciences (QE-Map). The grant is from NIH’s Biomedical Technology Research Resources (P41) program.

QE-Map will enable unprecedented insights into the role of metals and other inorganic (non-living) elements in human health and disease.

The Resource will be directed by Northwestern’s Thomas O’Halloran, the Charles E. and Emma H. Morrison Professor of Chemistry and Professor of Molecular Biosciences in the Weinberg College of Arts & Sciences.  The leadership team includes Chris Jacobsen, an Argonne Distinguished Fellow who is also Professor of Physics and Astronomy in the Weinberg College, as well as Professors Hao Zhang and Cheng Sun in the McCormick School of Engineering.

QE-Map will leverage Northwestern’s expertise in the areas of biophotonics, cell biology, inorganic chemistry, and X-ray physics, to pioneer cutting-edge imaging and detection technologies to deepen understanding of the interplay between metals and biological processes.

Thomas OHalloran

“Metal fluctuations play a critical regulatory role in a large number of biological processes,” says O’Halloran, the founding Director of CLP and the Director of Northwestern’s Quantitative Bioelement Imaging Center (QBIC).  “For example, fluctuations in the availability of zinc or copper can often be a trigger to the cell to change its function or developmental stage. A fluctuation in zinc might signal an egg to ovulate, or a second sperm, not to enter the egg. Too much manganese in the brain can trigger Parkinson’s disease. Pathological iron chemistry in the brain is involved in Alzheimer’s disease, and so on. These findings have generated a tremendous amount of interest across the fields of medicine, biology and physiology.”

Pioneering Testbeds for New Imaging Technologies

The Resource will support 75 faculty research programs, across Northwestern’s Schools of Medicine, Engineering, and College of Arts and Sciences, as well as collaborators from Argonne, Howard Hughes Medical Institute’s Janelia Research Center, Georgia Tech, Johns Hopkins, MIT, UC Berkeley, University of South Carolina, and University of Texas at Austin.  Investigators will provide the testbeds for new imaging technologies, tools, software, and quantitative methods for metal analysis and localization.  These new approaches will be applied to pioneering research in cardiac disease, fertilization and development, neurodegenerative diseases, and metabolic diseases.

“The ability to map metals and metal dynamics in the brain opens important new avenues in neuroscience research, for neurodevelopmental and neurodegenerative diseases but also for the fundamental understanding of how neurons communicate,” says Yevgenia Kozorovitskiy, Assistant Professor of Neurobiology at Northwestern. “The field has focused on calcium signaling in neurons for a long time, but zinc and other metals serve critical synaptic signaling roles in neurons that remain poorly understood, in addition to their functions as co-factors for important neuronal proteins.”

A new mass spectrometry tool operated by QBIC will enable rapid 2D and 3D imaging of cells in tissue slices. Advances will include development of a completely integrated system with real-time multi-element imaging capabilities, standardized procedures for handling cryogenically preserved biological tissues, and a universal cryo sample mounting system that can move between several different technologies that map and analyze elemental distributions.

Quantitative elemental maps of the mouse brain obtained via LA-ICP-TOF-MS: Green regions correspond to high concentrations of zinc, especially prevalent in the hippocampal formation. Blue regions correspond to copper enrichment in periventricular zones, and red areas indicate iron abundance. (Sample courtesy of the Kozorovitskiy and O’Halloran groups, analysis software from Tofwerk AG).

Faster and More Sensitive X-ray Imaging

The Resource will also employ large sample format Scanning X-ray Fluorescence Microscopy (SXFM), utilizing one of the nation’s brightest synchrotron radiation sources, the Advanced Photon Source, a U.S. Department of Energy Office of Science user facility located at Argonne National Laboratory.  The

Chris Jacobsen

SXFM will provide researchers with organ-wide information on metal distribution. Jacobsen, an expert in x-ray microscopy and trace metal quantitation, will lead efforts to increase the speed, cost-effectiveness and imaging sensitivity of SXFM, and standardize approaches for cryogenically preserving biological tissues for universal adoption across platforms.

“We want to push further the boundaries of what can be done with x-ray imaging and apply it to biological systems,” says Jacobsen, a member of Chemistry of Life Processes Institute. “The APS at Argonne is a great way to excite that x-ray florescence with a much higher rate and much higher spatial

resolution than ever could be done in a laboratory system.”

Ultrasonic Detectors that “Hear” the Sound of Color

A third Resource technology, Photo Acoustic Spectroscopy (PAM), is pioneered by Zhang and Sun. PAM deploys a highly novel, modular ultrasonic detector that combines a unique chemical process to image both frozen samples and live tissue at unprecedented resolution. This approach works by scanning a laser across a sample, causing heat and color intensity to increase, and triggering a shockwave that can be detected acoustically.  Cheng and Sun will work with collaborators to engineer molecular probes that cater to specific experimental needs. These advances will provide better ways to image time-dependent fluctuations in the concentrations of specific metal ions.

“It’s almost like hearing the sound of a color,” says O’Halloran. “There are disorders of the human brain where sensory inputs get confused between them, but in this case, we’re actually using the absorbance of a photon of a certain wavelength of light, which gives rise to the observation of a color, creating a sound wave that will help us localize an image in the material. By listening to the photo acoustic detectors, we can create a map from the sound pattern. It’s an incredible idea that has never been shown before.”

QE-Map will occupy a unique place among the 40 NIH-funded national resources as the only one advancing technology for studying the role of metals in health and disease.

“We will be collaborating with dozens of biomedical research teams from around country with the goal of understanding the molecular mechanisms at work in a variety of metal-linked diseases, from Wilson disease, Menkes disease, and Alzheimer’s, to Parkinson’s, heart disease, and diabetes,” says O’Halloran. “Each of the investigative teams around the country have a particular question in which they need to know how much metal is in their sample and what is it doing to the sample. We can help answer all those questions.”

This research resource is supported, in part by the National Institutes of Health 1P41GM135018-01 and 1S10OD26786-01. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

# # #

Contact:

Lisa La Vallee

Lisa.lavallee@northwestern.edu

National Center for Proteomics at Northwestern receives $7 million to expand impact

National Center for Proteomics at Northwestern receives $7 million to expand impact

Northwestern University received $7 million this year from the National Institute of General Medical Sciences to continue to push the boundaries of precision proteomics through new technologies and approaches to heart disease, cancer, neurological diseases and immuno-disorders, and to expand community engagement. The five-year grant builds upon the success of the National Resource for Translational and Developmental Proteomics (NRTDP), established in 2015 by Northwestern Proteomics, a center affiliated with Chemistry of Life Processes Institute.

“By providing far greater detail with next-generation technology, our national proteomics center is changing the fundamentals of how to read out proteins in basic and clinical research,” says Neil Kelleher, PhD, the Walter and Mary E. Glass Professor of Molecular Biosciences and Faculty Director, Northwestern Proteomics.  “This is increasing the efficiency of detection and assignment of function to proteins and their myriad modifications.”

The grant will enable major upgrades in technology for cell-specific analysis of whole protein molecules — an approach known as top-down proteomics.

Advancing Biomedical Research from SARS-CoV-2 and Cancer to Alzheimer’s

“In the past five years, we’ve been on the warpath to teach people about proteoforms,” said Paul Thomas, PhD, Research Associate Professor, Molecular Biosciences and Managing Director of Northwestern Proteomics. “Proteoforms are the individual modified protein molecules that exist in a biological system that may be responsive to, or causative of, diseases.”

The Center will advance dozens of translational research programs across Northwestern and other academic institutions that will focus on four key areas of research led by Jeannie Camarillo, PhD (Cancer Proteomics), Eleonora Forte, PhD (Immunoproteomics), Steven Patrie, PhD (Neuroproteomics), and John Wilkins, MD (Cardiac Proteomics).

Project collaborators will look at the proteomics of pediatric brain tumors, liver transplant rejection, aging, heart failure, and Alzheimer’s and Parkinson’s disease, to name a few.  These efforts, in turn, will drive technology development and applications for NRTDP’s new style of mass spectrometry-based proteomics.

“Despite decades of effort we have only begun to scratch the surface regarding the complex proteoform-level landscape of many disease-modifying proteins involved in neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease.” says Patrie, Research Associate Professor of Chemistry and Director of Neuroproteomics.  “With greater understanding of the composition and structure of proteins in the brain, as well as, the selectivity of diagnostics/therapeutics for families of proteoforms, the path to effective early diagnostics and disease-modifying therapeutics will undoubtedly become clearer.”

The Center is supported by “an exceptional group of research scholars” says Kelleher. In addition to Kelleher, Thomas, and the heads of the Center’s four research pillars, the leadership team includes:

  • Jared Kafader, Director of Instrumentation (incoming)
  • Phil Compton, Director of Instrumentation (outgoing)
  • Richard LeDuc, Director of Computational Proteomics
  • Robert (Vince) Gerbasi, Director of Immunoproteomics (outgoing)
  • Ryan Fellers, Director of Software Engineering
  • Young Ah Goo, Director of the Proteomics Core

Improved Testing for COVID-19

Proteoform-level analysis allows drug developers to find higher value biomarkers for disease, including COVID-19. Center researchers are working closely with Northwestern Feinberg School of Medicine investigators to understand how the human body generates antibodies to the SARS-CoV-2 proteins.

“We expect that our transplant patients, who all are on immunosuppression to maintain their transplanted organ, will respond differently to COVID-19,” says Feinberg investigator Daniela P Ladner, MD, MPH, Associate Professor of Surgery and Medical Social Sciences.  “Our collaboration with the Proteomics Center allows us to examine the antibody repertoire of COVID-19 positive transplant recipients.”

Expanding the Field

To encourage widespread adoption of top-down proteomics, NTDP offers a robust four-day training course for users of the Center’s core facilities located in Chicago and Evanston.  The Center also provides tools, materials, tutorials and exportable workflows enabling researchers among multiple disciplines and institutions to routinely access mass spectrometric measurements of their samples and proteins of interest.

“In its next five years, the Center will support over 100 laboratories at Northwestern and beyond, accelerating technology uptake via dissemination in the public and private sectors, and increasing the number of examples where proteoform-resolved biology provides clarity across a range of diseases,” says Kelleher.  “We’ve also spun out a new company, Integrated Protein Technologies led by Phil Compton, that will enable the field to continue to flourish and make significant advances in human health and disease.”

Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number P41GM108569. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

by Lisa La Vallee

Teri Odom honored by Royal Society of Chemistry

Teri Odom honored by Royal Society of Chemistry

Northwestern University chemist Teri Odom has received the 2020 Centenary Prize from the Royal Society of Chemistry.

The prestigious award, given annually to three chemists outside Great Britain, recognizes scientists for high-impact research and exceptional communications skills. The award comes with a £5,000 cash prize, a medal and an invitation to give a series of lectures in the United Kingdom.

Eric Anslyn of the University of Texas at Austin and James Tour of Rice University also received the Centenary Prize this year.

An expert in designing structured nanoscale materials, Odom received the award for her research into multi-scale materials that enable new ways to achieve ultrafast, coherent and directional light emission at the nanoscale.

“I’m very grateful to have received this award, not only to join the impressive ranks of previous recipients but also because of the breadth and inclusiveness of chemistry featured,” Odom said. “The celebration of a broad range of chemistry — that can also be clearly communicated — is pretty special and, at least to me, emphasizes the forward-looking nature of this award.”

Odom is the chair of Northwestern’s chemistry department and the Charles E. and Emma H. Morrison Professor of Chemistry in the Weinberg College of Arts and Sciences. She also is a member of Northwestern’s International Institute for Nanotechnology and the Chemistry of Life Processes Institute.

Odom’s research focuses on designing structured nanoscale materials with extraordinary size- and shape-dependent properties. She has pioneered a suite of multi-scale nanofabrication tools that have resulted in nanoparticle lattice optics that can manipulate light at the nanoscale, plasmon-based nanoscale lasers that exhibit tunable color and anisotropic nanoparticle probes for imaging.

Odom is a member of the American Academy of Arts and Sciences and a fellow of the Royal Society of Chemistry, the American Chemical Society, the Materials Research Society, the American Physical Society and the Optical Society of America. She is currently the editor-in-chief of Nano Letters.

Original story posted by Northwestern Now on June 25, 2020 by Amanda Morris.

‘Biotech by the Lake Investor Summit’ spotlights Northwestern cancer biotech ahead of ASCO

‘Biotech by the Lake Investor Summit’ spotlights Northwestern cancer biotech ahead of ASCO

On May 28, 2020, 300 investors, venture firms, pharma and biotech industry members and researchers, from across the US, Canada, China, UK and beyond tuned into the second annual Biotech by the Lake Investor Summit hosted by the Chemistry of Life Processes Institute (CLP) at Northwestern University, in partnership with Oppenheimer & Co. and BioCentury, Inc. The virtual conference, held the day before the American Society of Clinical Oncologists’ Annual Meeting, highlighted the latest cancer therapies and technologies pioneered by Northwestern investigators, as well as leading biotech companies, and panel discussions lead by industry insiders about the hottest trends and investment strategies for oncology biotech.

Thomas O’Halloran, PhD, the Founding Director of CLP, opened the program with a welcome and brief history of the Institute which celebrated its 10th anniversary in Silverman Hall this year.

A Launchpad for Drug Development

“The Institute was initiated as my colleagues and I began to realize that some of the most important applications in chemistry need to have a very deep partnership with biology, medicine and engineering,” said O’Halloran, the Charles E. and Emma H. Morrison Professor of Chemistry and Professor of Molecular Biosciences, Weinberg College of Arts & Sciences; Professor of Medicine, Feinberg School of Medicine.

O’Halloran described CLP as an interdisciplinary network of 66 institute investigators across 20 departments that have contributed to the launch of commercially successful drugs in many disease areas. He noted that, since its founding, the Institute has incubated 27 new companies raising $2.3B in total capital and helped to “lower the barriers between the disciplines and facilitate interaction with the investment and pharma communities.”

CLP’s Executive Advisory Board members, said O’Halloran, were “an extraordinary group of alums and professionals across the industry, neighbors, investors throughout the Chicago region who have a deep and abiding interest in promoting transdisciplinary research and facilitating the translation of new discoveries from the bench rapidly out to society.”

At the Forefront of Cancer Research

Three Northwestern faculty members gave presentations on innovations in cancer research. Nathan Gianneschi, PhD, Jacob and Rosaline Cohn Professor of Chemistry, Departments of Chemistry, Materials Science & Engineering, Biomedical Engineering and Pharmacology, discussed his work using protein-like polymers (PLP) as an effective delivery platform for peptide-based therapeutics. Josh Leonard, PhD, Associate Professor of Chemical and Biological Engineering; Charles Deering McCormick Professor of Teaching Excellence, presented his work developing new tools for engineering cell therapies through synthetic biology. Daniela Matei, MD, Diana, Princess of Wales Professor of Cancer Research; Professor of Medicine (Hematology and Oncology) and Obstetrics and Gynecology, Feinberg School of Medicine, provided an overview of her pioneering research into the significance of transglutaminase (TG2) and fibronectin (FN) protein complex, in cancer metastasis.

“We’re trying to find chemicals that would block a complex of two proteins which we believe are important in metastasis in ovarian cancer,” said Matei.  “People have never looked at it from this standpoint.”

Hottest Trends in Cancer Therapeutics and Technologies

The program then segued into a panel discussion about the hottest trends in cancer therapeutics and technologies led by Simone Fishburn, PhD, VP & Editor-in-Chief of BioCentury. Panelists included Andrew Chan, MD, PhD, Senior VP of Research Biology at Genentech, Neil Kelleher, PhD, the Faculty Director of Northwestern Proteomics, Elizabeth McNally, MD, PhD, Director, Center for Genetic Medicine; Elizabeth J. Ward Professor of Genetic Medicine in the Feinberg School of Medicine, and Nicholas Saccomano, PhD, CSO-SVP, Pfizer Boulder Research and Development.  Chan is the chair of of CLP’s Executive Advisory Board.

Panelists touched upon topics ranging from immune checkpoint inhibitor (ICI) development, the future of small molecule kinase inhibitors, to the applications of revolutionary gene editing approaches and proteomics in oncology.

“There’s been a lot of advances in biology and technologies to advance the field of cancer immunotherapy. One of the recent advances is tiragolumab, a novel cancer immunotherapy designed by Genentech/Roche, that binds to TIGIT, an immune checkpoint protein expressed on immune cells,” said Chan, a member of CLP’s Executive Advisory Board. “The impact of the first wave of cancer immunotherapy with PD1/PD-L1 has revolutionized the treatment of melanoma, renal cell, lung and made inroads in breast metastatic cancers.” Chan noted that the company is embarking on multiple phase 3 clinical programs that are “just the tip of the iceberg.”

Breakthroughs in the Pipeline

Three senior biopharma executives provided updates on their companies’ lead cancer therapies.  Barbara Klencke, MD, Chief Development Officer, Sierra Oncology (SRRA) described the clinical stage drug development of momelotinib, a potent, selective and orally bioavailable JAK1, JAK2 & ACVR1 inhibitor, for the treatment of myelofibrosis. Mani Mohindru, PhD, CEO, CereXis and a member of CLP’s Executive Advisory Board, discussed the biotech company’s progress on promising treatments for rare brain tumors, such as Neurofibromatosis 2 (NF2). Jonathan Zalevsky, PhD, Chief Research and Development Officer, Nektar (NKTR), detailed the company’s diverse pipeline, including its lead candidate bempeg, a CD122-preferential interleukin-2 (IL-2) pathway agonist which, in combination with nivolumab, is currently in pivotal Ph3 trials in adjuvant treatment of melanoma and invasive bladder cancer.

Investing in Chicago’s Life Sciences Ecosystem

The program wrapped up with a panel discussion on financing and investing in oncology biotech led by Jay Olson, CFA, Research Analyst with Oppenheimer & Co. Olson provided analysis on trends in FDA approvals, IPOs, and M&A activity. Vanessa Bhark, Senior Associate, Frazier Healthcare Partners, Maha Katabi, PhD, CFA, General Partner, Sofinnova Investments, Michael Margolis, RPh, Managing Director, Oppenheimer & Co, and Alex Munns, Assistant Portfolio Manager, Senior Analyst Driehaus Capital, participated in the discussion.

“We have fantastic academic centers in Chicago and a growing sense of the financial capabilities of some of the groups, including ours here in Chicago,” said Munns. “I’m excited to continue to build Chicago into a thriving ecosystem in the life sciences that will make it look more on par with what our colleagues and friends in Boston, San Francisco and New York are doing.”

Click below to view the event recording:

Read Oppenheimer’s detailed report: “Stars Align at CLP Biotech Summit—Highlights from Our 2nd Annual Event.”

By Lisa La Vallee

 

 

 

Mechanism behind upper motor neuron degeneration revealed

Mechanism behind upper motor neuron degeneration revealed

Scientists from Northwestern Medicine and the University of Belgrade have pinpointed the electrophysiological mechanism behind upper motor neuron (UMN) disease, unlocking the door to potential treatments for amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases, such as Hereditary Spastic Paraplegia and Primary Lateral Sclerosis.

The study, published in Frontiers in Molecular Neuroscience on May 19, 2020, reveals the molecular underpinnings of electrical signals from potassium and sodium ion channels within the neuron’s cell membrane.

Maintaining stability is the primary goal of healthy UNMs. Without it, cells begin to degenerate. Like the game of telephone, when UMNs process signals from neighboring neurons incorrectly, the message fails to reach the motor neurons in the spine, which instruct muscles to move.

“Voltage-gated ion channels, as a family, are involved in many neurodegenerative diseases, but their function, modulation, and expression profile are very complicated,” said senior study author Hande Ozdinler, associate professor of neurology at Northwestern University Feinberg School of Medicine.

To identify the precise areas within the ion channels where the dysfunction began, the investigators, led by Dr. Marco Martina, associate professor of physiology and of psychiatry and behavioral sciences at Feinberg, recorded the electrical signals of in vivo cells in the earliest stage of ALS to measure the neuron’s reaction to external stimuli. The team also looked at the genes of the diseased UMNs’ ion channels to measure the changes in the structure of the ion and its subunits to determine whether the cause of degeneration was intrinsic.

The data revealed that early in the disease UMNs were unable to maintain the balance of excitation and inhibition within the cortical circuitry and their behavior was due to dynamic changes in key ion channels and their subunits.

“We all knew ion channels were important, but we did not know which ion channel or which subunit was pivotal for shifting balance from health to disease in UMNs,” said Ozdinler, a member of the Chemistry of Life Processes Institute. “When we received the exon microarray results, it was obvious that the ion channels were perturbed very early in the disease, potentially initiating the first wave of vulnerability.”

By identifying the molecular underpinnings of the early stages of neurodegeneration, the study also identified potential targets for future treatment strategies.

“There are already drugs out there for some of those ion channels and subunits, but we never thought that we could use them for ALS because we did not know the mechanism,” said Ozdinler. “This is the information we needed to move forward. “Now, we may begin to investigate whether we can utilize some of these drugs, already approved by the FDA, for motor neuron diseases.”

Pavle R. Andjus, a faculty member of Biology University of Belgrade in Serbia, is a co-author of the study.

“At the end of the day it was persistence and friendship that allowed us to make this discovery happen,” said Ozdinler. “I think if we team up and walk extra mile there isn’t any discovery we cannot make.”

This work was funded by NIA-RO1AG061708, Les Turner ALS Foundation, National Institutes of Health (NIH) grant NS066675, Amyotrophic Lateral Sclerosis Association Milton Safenowitz Postdoctoral Fellowship, and European Commission H2020 MSCA RISE grant 778405.

by Lisa La Vallee

lisa.lavallee@northwestern.edu

One-step diagnostic tool receives NSF RAPID grant

One-step diagnostic tool receives NSF RAPID grant

Northwestern University synthetic biologists have received funding to develop an easy-to-use, quick-screen technology that can test for infectious diseases, including COVID-19, in the human body or within the environment.

Similar to a pregnancy test, the tool uses one sample to provide an easy-to-read negative or positive result. By simplifying testing, the researchers could put diagnostics into the hands of people everywhere — without the need for expensive laboratories or expertise. This could provide the large-scale testing required for ending stay-at-home orders, reopening the economy or preparing for a predicted virus resurgence in the fall.

The team is working to develop and optimize the test so that it will be a single step, taking less than an hour to provide a result and less than a dollar to manufacture.

On Friday, the project received a rapid response research (RAPID) grant from the National Science Foundation (NSF), which has called for immediate proposals that have potential to address the spread of novel coronavirus (COVID-19). The grant provides $200,000 over one year.

“The current COVID-19 pandemic highlights the limitations of laboratory-based testing,” said Northwestern’s Julius Lucks, the principal investigator on the project. “Those tests have not scaled with the sudden and dramatic increase of needed volume. They require too much equipment, time, expertise and infrastructure, which have resulted in major logistical challenges and, ultimately, inadequate testing. It’s become clear that we need to dramatically increase the scale of testing to safely restart the economy, to provide critical information if the virus resurges and to provide monitoring to prevent this in the future.”

Lucks devised the project with fellow Northwestern Center for Synthetic Biology (CSB) members Michael JewettJoshua Leonard and Niall Mangan. Jewett and Leonard are professors of chemical and biological engineering in Northwestern’s McCormick School of Engineering; Mangan is an assistant professor of engineering sciences and applied mathematics in McCormick. They have partnered with Khalid Alam, a former postdoctoral fellow in Lucks’ laboratory and CEO of Stemloop, Inc., which spun out of the CSB to commercialize rapid, field-deployable synthetic biology diagnostics technologies.

“Over the past few years, we have pioneered the use of cell-free systems as easy-to-use, point-of-need diagnostics,” said Jewett, director of the CSB. “These field-deployable systems can sense a variety of contaminants relevant to public health, including lead, fluoride and atrazine. We are trying to use that know-how to help address gaps in COVID-19 testing.”

The test works by combining gene-editing tool CRISPR, custom genetic circuits and cell-free synthetic biology in order to detect the virus and signal its presence. The team envisions that the final product could test patients’ samples from a nasal swab or saliva sample as well as water and surfaces in the surrounding environment.

“As far as we know, this is the first diagnostic tool to confront environmental monitoring,” Lucks said. “We could use this technology to monitor the presence of the virus on surfaces or even in the water. Recent research suggests that monitoring wastewater might provide clues about viral spread. Given the broad-scale need, we also plan to aim for clinical applications.”

After the test is developed in the laboratory, Stemloop will quickly transition the technology for manufacturing, deployment and distribution. The researchers aim to have the test ready for the novel coronavirus’ predicted resurgence in the fall. The tool, however, also can be rapidly reprogrammed to detect new emerging pathogens for future pandemics.

Lucks, Jewett and Leonard are members of Northwestern’s Chemistry of Life Processes Institute. Jewett and Leonard are members of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. Alam is an entrepreneur in Argonne National Laboratory’s Chain Reaction Innovations program.

Editor’s note: Lucks and Jewett have financial interests in Stemloop Inc.

Original story posted by Northwestern Now on April 20, 2020 by Amanda Morris.

Biodistribution of new ACE2 therapeutic visualized by SPECT imaging

Biodistribution of new ACE2 therapeutic visualized by SPECT imaging

Northwestern Professor Daniel Batlle, Earle, del Greco, Levin Professor of Nephrology/Hypertension in the Feinberg School of Medicine, is working on using shorter forms of Angiotensin-converting enzyme (ACE2) as a therapy for kidney diseases. The devastation of COVID-19 has pushed many researchers to think of ways to treat patients by borrowing therapies and ideas from similar viruses like SARS-CoV (2002-2004) and Ebola. ACE2 has been demonstrated to be the main receptor for the spike protein in SARS-CoV and recently SARS-CoV-2. The soluble, i.e. shorter, ACE2 molecule developed by Batlle and Wysocki could be used as a competitive interceptor of SARS-CoV-2, thereby preventing infection (Main Image).

In Figure 2, radiolabeled ACE2 is used to compare distribution of a soluble short ACE2 (left) and full size soluble native ACE 2 (right).  Chemistry of Life Processes Institute’s Center for Advance Molecular Imaging provides state-of-the-art Single Photon Emission Computed Tomography (SPECT) imaging to visualize differences in the two ACE2 molecules. Although Figure 2 is a 2D presentation of the data, SPECT provides quantitative, in vivo, noninvasive, 3D data.

References:
Soluble Angiotensin-Converting Enzyme 2: A Potential Approach for Coronavirus Infection Therapy? Daniel Batlle, Jan Wysocki, Karla Satchell Clin Sci (Lond) 2020 Mar 13;134(5):543-545. doi: 10.1042/CS20200163. PMID: 32167153 DOI: 10.1042/CS20200163

Cell-free biotechnology could help accelerate COVID-19 therapeutics

Cell-free biotechnology could help accelerate COVID-19 therapeutics

When it comes to fighting a fast-spreading pandemic, speed is critical.

Researchers at Northwestern and Cornell Universities have developed a new platform that could produce new therapies more than 10 times faster than current methods. The secret behind the platform’s unmatched speed is an unlikely tool: bacteria.

After taking the molecular machinery out of bacteria, the researchers then use that machinery to make a product, such as therapeutics, in a safe, inexpensive and rapid manner. The idea is akin to opening the hood of a car and removing the engine, which allows researchers to use the engine for different purposes, free from the constraints of the car.

Through their startup company, SwiftScale Biologics, the Northwestern and Cornell researchers are working to mass produce a promising antibody therapy developed by an outside biotherapeutics company. The antibody binds to the part of the coronavirus that infects the host cells, stopping it in its tracks.

“Everything is moving so incredibly fast, and this is an urgent problem,” said Northwestern’s Michael Jewett. “We believe that cell-free biomanufacturing can cut production times of antiviral medicines to the timescale of just a few months rather than closer to a year. This could help us address the current outbreak.”

Michael Jewett

Jewett is a professor of chemical and biological engineering in the McCormick School of Engineering and director of Northwestern’s Center for Synthetic Biology. He co-founded SwiftScale Biologics with Matthew DeLisa, the William L. Lewis Professor of Engineering at Cornell and director of the Cornell Institute of Biotechnology, and David Mace from 8VC.

The team had been using the synthetic biology-based platform to mass manufacture potential protein therapeutics for cancer. But it quickly pivoted to leverage the technology to help address the novel coronavirus (COVID-19) pandemic, for which no reliable treatment yet exists.

“Since the COVID-19 outbreak, we have dedicated nearly all of our resources to producing an antiviral therapy to fight it,” Jewett said. “Specifically, we are designing simplified antibody-based drugs that can be produced in bacteria rather than mammalian cells, which are far slower and more expensive to scale. In this way, we believe that we will be able to get a COVID-19 treatment into the clinic and ultimately to affected patients worldwide more quickly while increasing access.”

The SwiftScale Biologics team is currently engineering bacterial strains with increased production levels of previously discovered SARS-CoV antibodies as a test case. Next week, the team will test the bacterial strains to produce antibodies for COVID-19. This material will be used for animal studies to confirm the drug’s safety before entering human clinical trials, potentially as soon as this summer.

Jewett is a member of Northwestern’s Chemistry of Life Processes Institute and the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

Editor’s note: Jewett has financial interests in SwiftScale Biologics. Northwestern University has financial interests (equities, royalties) in SwiftScale Biologics.

Original story appeared in Northwestern Now on April 2, 2020 by Amanda Morris.

Jewett and Gianneschi named elite medical and biological engineering fellows

Jewett and Gianneschi named elite medical and biological engineering fellows

Northwestern Engineering’s Michael Jewett and Nathan Gianneschi have been elected to the American Institute for Medical and Biological Engineering’s (AIMBE) College of Fellows.

AIMBE’s College of Fellows comprises the top 2 percent of medical and biological engineers in the country. Fellows are recognized for their notable contributions advancing the fields of medical and biological engineering through research, practice, or education.

Jewett and Gianneschi are among 156 engineers who make up the College of Fellows Class of 2020. They were formally inducted remotely on March 30.

Jewett, Walter P. Murphy Professor of Chemical and Biological Engineering, is an expert on cell-free synthetic biology, protein synthesis, therapeutics, glycosylation, and engineered ribosomes. He is developing cell-free biology as an enabling technology for biomanufacturing lifesaving therapeutics, sustainable chemicals, and novel materials, both quickly and on-demand.

Michael Jewett

The director of Northwestern’s Center for Synthetic Biology, Jewett was elected to AIMBE for “outstanding contributions to develop cell-free synthetic biology and repurpose translation for on-demand biomanufacturing, portable diagnostics, and education kits.”

Jewett recently introduced a system that can rapidly create cell-free ribosomes in a test tube, then select the ribosome that can perform a certain function. The platform could help enable new manufacturing approaches to sustainable materials and targeted therapies.

Nathan Gianneschi

Gianneschi, the Jacob and Rosalind Cohn Professor of Chemistry in the Weinberg College of Arts and Sciences and professor of materials science and engineering and biomedical engineering at the McCormick School of Engineering, studies how nanomaterials interact with cells, tissues, and biomolecules, with an interest in synthetic materials programmed with biopolymers as delivery systems. His research group also develops responsive materials and “smart” nanoparticles as well as new techniques for the discovery of functional nanomaterials and bionanomaterials through library screening methodologies.

He was recognized by AIMBE for “pioneering and creative contributions to nanomedicine through the invention of bioresponsive phase-change materials for selective tissue targeting.”

Last year, Gianneschi developed a new drug-delivery system that disguises chemotherapeutics as fat in order to penetrate and destroy tumors. The system tricks tumors into inviting in the chemotherapeutic, which then activates the targeted drug and immediately suppresses tumor growth.

Original story appeared in Northwestern Engineering News on March 30, 2020 by Alex Gerage.

Michael Jewett and Nathan Gianneschi are both members of the Chemistry of Life Processes Institute. Jewett is also co-director of CLP’s Recombinant Protein Production Core.

New drug target found for COVID-19

New drug target found for COVID-19

A new potential drug target has been identified in SARS CoV-2 — the virus that causes COVID-19 — by scientists who say multiple drugs will likely be needed to respond to the pandemic.

Scientists from Northwestern University Feinberg School of Medicine have mapped the atomic structure of two critical proteins in a complex, nsp10/16. These proteins modify the genetic material of the virus to make it look more like the host (human) cell RNA.

This allows the virus to hide from the cells, giving it time to multiply. If a drug can be developed to inhibit nsp10/nsp16, the immune system should be able to detect the virus and eradicate it faster.

“This is a really beautiful target, because it’s a protein absolutely essential for the virus to replicate,” said lead investigator Karla Satchell.

Satchell is a professor of microbiology-immunology at Northwestern and director of Center for Structural Genomics of Infectious Diseases (CSGID), an international consortium of scientists who are investigating the structure of the virus to aid drug development.

Satchell’s team is sending the new protein to Purdue University, the drug-discovery site of the center, to be screened for novel inhibitors that could be developed as new drugs.

The nsp10/nsp16 protein is called an RNA methyltransferase or MTase. It is comprised of two proteins bound together, which makes it more difficult to work with. The association of the two pieces together is required to make a functional protein, according to prior research on SARS.

The structure of nsp10/16 was released to the scientific community March 18 on the RSCB Protein Data Bank.

This is the fourth protein structure of a potential drug target of SARS-CoV-2 determined by the CSGID team of scientists.

“We need multiple drugs to treat this virus, because this disease is likely to be with us for a long time,” Satchell said. “It’s not good enough for us to develop a single drug. If COVID-19 develops a resistance to one drug, then we need others.”

The center is racing to release more structures for drug development. The center’s goal is to determine structures of all of the proteins that are potential drug targets. The team also is collaborating to provide proteins to investigators for design of improved vaccines.

Data for this structure was collected at the Northwestern managed Life Sciences Collaborative Access Team beamline at the Advanced Photon Source at Argonne National Labs. The LS-CAT staff worked quickly with APS and Satchell to provide rapid access to the beamline over a weekend specifically to collect data for this project.

“The center has shown a great ability to bring structure biology to the scientific community at an unprecedented rate,” Satchell said. But their work has become more challenging because so many universities have reduced activities and some labs have shut down entirely.

“Our ability to do experiments is abating,” Satchell said. Still, the center will continue to release new structures until they reach their goal, she said.

Structures of three other proteins important for the replication of the virus have also been released:  the nsp15 endonuclease, nsp3 ADP ribose phosphate and nsp9 replicase. These structures were determined by the center scientists at University of Chicago headed by professor Andrzej Joachimiak, Distinguished Fellow of Argonne, who also is an adjunct professor at Northwestern. All work conducted by both the University of Chicago and Northwestern teams was designed by the bioinformatic team of Adam Godzik at the University of California at Riverside, based on research conducted in SARS.

The CSGID is supported by a contract from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, in part to serve as a response site to conduct structure biology research in the event of an unexpected infectious disease outbreak. NIAID has been working closely with the Center since early January to coordinate center activities with other research supported by NIAID to enable drug discovery.

This study has been funded by contract HHSN272201700060C from the National Institute of Allergy and Infectious Diseases, part of the NIH.

The original story was published in Northwestern Now on March 27, 2020 by Marla Paul.

Postscript:

Purification of the protein targets identified by Satchell and team was conducted by Chemistry of Life Processes Institute’s Recombinant Protein Production Core.  The rPPC provides quality controlled recombinant proteins for Northwestern researchers as well as academic and industry researchers outside of the University, including CSGID scientists. 

According to rPPC Managing Director Sergii Pshenychnyi, rPPC produced two SARS-CoV-2 proteins, SARS-CoV-2 papain-like protease (PLpro) and chymotrypsin-like protease (3CLpro)  for CSGID and sent them to Purdue University for the purpose of testing possible drugs that inhibit the proteases central to the function of the virus.

“Data suggests that some of the compounds that made it through early stage clinical trials may be working,” says Pshenychnyl. “The process, however, will take months (possibly a year) of subsequent drug development.”

Pshenychnyl is also working with Daniel Batlle Group (FSM, Nephrology and Hypertension Department) to purify the human angiotensin-converting enzyme 2 (hACE2). SARS-CoV-2 enters the human body by binding to hACE2.  He is also working on another project for Pablo Penaloza (Department of Microbiology and Immunology), producing receptor binding domain of SARS-CoV-2, Wuhan-Hu-1 Spike Glycoprotein in HEK293 cells. Both will be used to perform critical vaccine studies.

 

Structure revealed of key chromatin-remodeling complex

Structure revealed of key chromatin-remodeling complex

Northwestern University researchers have mapped a group of proteins that play a critical role in both gene expression and repairing damaged DNA. By understanding this protein complex, called SWI/SNF, researchers hope to better understand how cancer arises.

SWI/SNF regulates the structure of chromatin, which comprises genetic material in a cell’s nucleus and often mutates as cancer develops.

“Mutations of this essential complex have been found in more than 20 percent of all human cancers associated with a wide range of tissue types,” said Northwestern’s Yuan He, who led the study. “Understanding the molecular mechanism of the SWI/SNF complex in regulating chromatin structure and gene transcription is thereby essential for a complete understanding of how chromatin structure alterations lead to cancer.”

Yuan He

The paper was published today (March 11) in the journal Nature. Yuan He is an assistant professor of molecular biosciences in Northwestern’s Weinberg College of Arts and Sciences.

To determine the unique structure, the He lab used cryogenic electron microscopy (cryo-EM), a powerful technique capable of revealing the 3D shape of large protein complexes. The technique involves flash-freezing proteins at a speed where water molecules don’t have time to re-organize to form crystalline ice. These protein complexes are then directly imaged by an electron microscope, and their 3D shape can then be reconstructed in 3D using a supercomputing cluster. Before cryo-EM, researchers mainly used X-ray crystallography, which is incapable of capturing high-resolution images of important complexes such as this.

This landmark study is the first time that researchers have used cryo-EM to determine the SWI/SNF structure bound to a nucleosome, at near-atomic resolution. “cryo-EM is a revolutionary technique,” said Carole LaBonne, chair of the Department of Molecular Biosciences. “It is taking over in the critical field of structural biology. Every major research university is making major investments in this field because it is clear that it holds the key to unraveling many unanswered questions in biomedical science.”

Professor Yuan He explained that the structure will allow researchers to map and rationalize cancer-related mutations in the human SWI/SNF complex.

He added that the study will provide the molecular platform for better understanding the important functions of SWI/SNF in both healthy and cancerous states, as well as for developing potential therapeutic strategies for human malignancies.

“Our study gives insight into how the complex suppresses tumor development,” He said. “And it  could contribute to developing therapeutics for cancers harboring mutations in genes encoding the SWI/SNF complex.”

The study, “Cryo-EM structure of SWI/SNF complex bound to a nucleosome,” was supported by a Cornew Innovation Award from the Chemistry of Life Processes Institute at Northwestern University, the American Cancer Society (award number IRG-15-173-21) and the National Institutes of Health (award number R01GM135651, P01CA092584, U54CA193419 and 5T32 GM008382).

The original story was published in Northwestern Now  on March 11, 2020 by Rebecca Lindell.

Yuan He is a member of the Chemistry of Life Processes Institute.