College of Science Connects: Research at the Frontier of Bioanalytical Chemistry

Join Hazel Sive, Dean of the College of Science, as she talks to Leila Deravi, Assistant Professor of Chemistry and Chemical Biology for the Barnett Institute for Chemical & Biological Analysis.

Professor Deravi is one of the leading faculty members at the Biomaterials Design Group. Prof. Deravi investigates fundamental mechanisms behind systems in biology and to better inform the design of new classes of protein-based biomaterials that may interface with or enhance the performance of humans.

Register here: http://bit.ly/2N5By2w

 

Matz Scholars: Investing in Excellence, Investing in the Future

If you’re looking to learn more about Bob Matz ‘62, you’re probably not going to find what you’re looking for here.  Bob would much rather spend his time talking about the student scholars in Northeastern’s Biotechnology Co-op Research Fellowship Program. Along with his wife Eileen, Bob has generously and proudly supported nearly 70 undergraduate students from the College of Science working for 6 months in world-class labs on campus and around Boston.

Bob is a graduate of Northeastern University’s College of Liberal Arts. At the time of his attendance, Northeastern was a long-celebrated engineering school, and he recalls that he and his fellow science students “were a much smaller group.” Bob, whose love of science is palpable, admits that as an undergrad, at some point, he felt a bit unfulfilled in the teaching lab. He likens the experience to reading a cookbook. “I was just mixing up the ingredients and making exactly what the person before me had made,” says Bob. “It just wasn’t interesting to me. I realized later in life how thrilling it would have been to have worked in a real world-class lab as a 2nd or 3rd year student.”

The fellowship co-op program aims to not only provide that educational thrill of working in a research facility, but also pairs the student with the mentorship of a faculty member – a relationship that extends beyond the classroom. And, the impressive group of young scientists who have benefited from Bob’s steadfast belief in experiential learning are the proof.  “These students are bright and articulate and ready to accomplish something great.,” says Bob. “They have all the capabilities.” And, accomplishing things is exactly what they are doing.

Graduates have gone on to impressive careers in medicine, research and industry.  “The Matz Scholarship was critical for my career as a researcher. The scholarship allowed me to gain extensive experience conducting research in an academic laboratory, including designing and running experiments, analyzing and sharing my results in lab meetings, and presenting a poster at an international conference, “ says Lauren Byrnes ’13 (Biology). “These experiences led to my decision to pursue a career in science research and to apply for a master’s, and later, a PhD program. I am very grateful for the opportunities granted to me through the Matz Scholarship.”

“As a Matz Scholar, I was empowered to conduct cutting-edge research with remarkably intelligent, diverse, and kind individuals who helped lay the foundation for my current career in science, “ says David Hill ’14. “Without the Matz Program, I would have not been able to reach my true potential as a scientist.” And, it’s that potential that compelled Bob to start the fund. He believes in the importance of students having the opportunity to use the Scientific Method to accomplish something of quality and usefulness and that in doing so, it will further fuel their enthusiasm and excitement for science.

Bob’s love for science and scientists runs pretty deep.  Initially, his engagement with Northeastern as an alum was minimal as he established his career and started a family.  But, he did keep in touch with Dr. Riser, an influential professor during his time at Northeastern, and his roommate Dr. Sol Katz, who completed his co-op under the tutelage of Don Comb, the founder of New England Biolabs and went on to be a science professor at University of Pennsylvania.  He enthusiastically describes them as “pure scientists” and has obvious great admiration for them. He also worked for many years alongside Barry Karger and Louis Barnett as a biotechnology consultant to Northeastern’s Barnett Institute of Chemical and Biological Analysis and considers them good friends and brilliant scientific minds. He credits these relationships with inspiring him to establish the fellowship.  “The students learn valuable skills about working with a team – they work with post-docs, grad students, techs, faculty and other students,” says Bob.  “They learn how gratifying it is to be one part of something bigger than just you.”

This year, Bob has enhanced his commitment to giving to Northeastern with additional funding to support student co-ops at the Ocean Genome Lab (OGL). This is an endeavor near to his heart and a way of honoring his dear friend and dedicated scientist, New England Biolabs and OGL founder Don Comb, who passed away earlier this year. Bob encourages his fellow alums to find ways to support students in science because as he says, “It’s better than cement! I’d much rather see the sparkle on a young student’s face and feel the warmth of furthering their learning experience than see my name on a door.”

Congratulations to this year’s Biotechnology Co-op Research Fellowship honorees:

Fatemah Mukadum, ’22 (Chemistry)
“Searching for light-promoted cancer therapeutics with quantum chemistry and machine learning”
Research Advisor: Steven Lopez, PhD

Benjamin Rich, ’21 (Chemistry)
“Method Development for Copper II Chelation Ligand Testing”
Research Faculty Advisor: Rein Kirss, PhD

Hoang Yen Vu, ’21 (Biochemistry)
“Function prediction for host and symbiont proteins in a bivalve mollusk: Can these creatures guide us to biotech production of biofuels?”
Research Faculty Advisor: Mary Jo Ondrechen, PhD

Big Ideas from a Small Scale: Professor Alexander Ivanov is Changing the Power of Proteomics

Uncovering the innerworkings of biological and chemical mechanisms is necessary for research breakthroughs—there are no new drugs without understanding how proteins interact with the body and synthesized pharmaceuticals. There would be no COVID-19 vaccine without the knowledge of the structure of the protein and the function of the protein in our bodies. This knowledge derives from and relies on the ever-growing field of proteomics, or the large-scale study of proteins, in which thousands of proteins are characterized in biomedical samples. Though powerful, proteomics can be limited by many factors—sensitivity of the instrumentation (mass spectrometers, for example), and size and complexity of the sample. Professor Alexander Ivanov and his lab are pushing those limits.

Recently, Ivanov was awarded the Outstanding Investigator Award (R35) by the National Institutes of Health (NIH). The grant of over $2 million advocates for experienced researchers taking on long-term projects with potentially impactful results.

Ivanov’s research is nothing short of impactful. “One of the possible research directions is to increase the sensitivity and the depth of overall proteomic profiling to enable characterization of individual single cells picked from either suspension or tissue samples,” said Ivanov about the proposal he submitted for the grant. “Also, possible clinical applications when we just have a few cells available, like a microneedle biopsy for example, or 3-D cultured cell lines in very small formats, organoids, where only a few cells are available.”

While proteomics can change the ways we understand biology by characterizing post-translational modifications and protein-protein or protein-ligand interactions (areas where genomics cannot reach), some common misconceptions is that proteomics lacks quantitative and reliable results and fails to analyze small-scale samples. Ivanov’s research focuses on optimizing the field by creating high sensitivity technologies, modifying sample preparation methods, and developing sophisticated mass spectrometry data acquisition and analysis techniques, all of which leave those misconceptions to the wind.

Ivanov is looking to the future, especially with the many benefits of the Outstanding Investigator Award. “This program provides a lot of flexibility,” said Ivanov. “If we see new opportunities in biomedical research enabled by the technologies we are developing for characterization of limited samples, we can easily expand from the outlined research aims…We can accommodate new milestones and new directions.”

His research will be powerful in expanding the use of proteomics—these techniques can be applied to understanding limited and rare cell populations, such as circulating tumors cells, hematopoietic stem cells, and immune cells buried deep in small biological samples, as his grant project summary details.

Ultimately, Ivanov looks forward to expanding upon his life’s research and continuing his work within the Northeastern community through the aid of the Outstanding Investigator Award. “In my research and my educational efforts, I work a lot with graduate students, undergraduate students, post-docs, research scientists. We have collaborative programs across colleges and within our College of Science. I work with a diverse pool of students and they are an amazing resource here at Northeastern. Students and post-docs make this work possible!”

Alexander Ivanov

Collaborative Agreement with AB Sciex

Sunny Zhou

Professor Zhaohui Zhou (pronounced like Joe), a.k.a. Sunny, received his B.S. in chemistry from Peking University, Ph.D. in bioorganic chemistry from The Scripps Research Institute under Professor Donald Hilvert (now at ETH), and did postdoctoral research in enzymology and biochemistry with Professor Rowena G. Matthews at the University of Michigan. He is an editor of the journals mAbs and Therapeutic Antibodies.

Jeffrey Agar

The Agar group characterizes post-translational modifications of proteins and changes in protein, peptide, and lipid expression that occur during ALS, and then determines which of these changes have structural or toxic consequences. Because ALS begins with the death of a single type of cell, the motor neuron, we have developed numerous methods for the analysis of single cells by mass spectrometry. The Agar group specializes in mass spectrometry, including ultra-high mass resolution “top-down” mass spectrometry and mass spectrometry imaging methods, and has developed both analytical methods (“Matrix solution fixation” introduced by Agar YR 2007, automated funnel-skimmer dissociation, Karabacak 2008 and Cobb 2010, single-cell mass spectrometry imaging of mammalian cells, Agar YR 2010 and Boggio 2011) and computational tools (Karabacak 2008 introduced “Big Mascot” or Mascot TD database search engine, Li 2008 and 2010 introduce isotope calculator, a suite for mass spectrometry imaging applications is functional and to-be-submitted).

Prof. Agar is a joint appointment between the College of Science and the Bouvé College of Health Sciences.

Heather Clark

Heather Clark is a Professor in the Departments of Bioengineering and Chemistry at Northeastern University. She received her PhD in Analytical Chemistry from the University of Michigan, and completed a postdoc in the Center for Cell Analysis & Modeling at the University of Connecticut Health Center. Dr. Clark’s research focuses on the development of nanosensors to measure concentrations of ions and small molecules at the cellular level, as well as in vivo. She has received awards for both research and teaching, including the DARPA Young Faculty Award. Her work has been featured in a live CNN interview, the Wall Street Journal, WIRED magazine and MIT Technology Review.

Alexander Ivanov

Prof. Ivanov earned his Ph.D. in Bioorganic Chemistry at the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Science, Moscow in 2000.  He initially joined Northeastern University as a postdoctoral fellow at the Barnett Institute (2000 – 2003).  Then he joined Harvard University first as Assistant Director and then he was promoted to Associate Director of the Harvard NIEHS Center for Environmental Health Proteomics Facility at the Department of Genetics and Complex Diseases (GCD) of the Harvard School of Public Health (HSPH).  Dr. Ivanov continued his tenure at Harvard University becoming Director of the HSPH Proteomics Resource in 2008.  Dr. Ivanov re-joined Northeastern as Research Associate Professor at the Barnett Institute of Chemical and Biological Analysis in 2011.  In 2017, he accepted a position of an Associate Professor at the Department of Chemistry & Chemical Biology and Faculty Fellow at the Barnett Institute of Chemical & Biological Analysis.

Prof. Ivanov’s research focuses on the development of microscale liquid phase separation- and mass spectrometry (MS)-based proteomic technologies for solving challenging biomedical problems. The areas he is currently working on include: (1) deep proteomic profiling of limited biological samples (e.g., rare circulating cells, microdissected cells from tissue microscale biospecimens) using ultra-low flow liquid phase separation techniques, including capillary electrophoresis (CE) and ultra-narrow bore column liquid chromatography (LC) interfaced with advanced MS; (2) comprehensive characterization of protein isoforms, modifications (e.g. post-translational modifications, chemical modifications, sequence variants, charge variants), and protein complexes (in their native non-denatured states), including characterization of biopharmaceuticals, using a combination of bottom-up, middle-down, top-down and native proteomic approaches; (3) development of ultra-low flow liquid phase separation techniques, including CE and ultra-narrow monolithic and porous layer open tubular column LC for high sensitivity (attomole and low zeptomole level) MS analysis; and (4) isolation and characterization of extracellular vesicles, including circulating exosomes and microparticles, as potential sources of biomarkers for disease diagnostics and therapy delivery vehicles. He has been actively involved in national and international initiatives enabled under the umbrella of the ABRF to develop standards for proteomics research and standardize proteomic practices. Dr. Ivanov’s expertise involves advanced sample preparation, liquid phase separation, MS and bioinformatics techniques.

John Engen

Current research projects in his laboratory include (1) investigations of kinase conformation to understand regulation and aberrant signaling in various disease states including cancer, (2) analysis of the conformation of viral accessory proteins from HIV, (3) studies of protein conformation at biological membranes, and (4) optimization and methods development in hydrogen exchange mass spectrometry.

Leila Deravi

The Biomaterials Design Group at Northeastern University works at the interface of bio-analytical chemistry, materials science, and design. We investigate fundamental mechanisms behind systems in biology and use our understanding to better inform the design new classes of protein-based biomaterials that may interface with or enhance the performance of humans. Thus, a key aspect of our research is developing strategies to build the structure dependent function of biomolecules into macromolecular materials. A summary of our ongoing projects to support this goal are described here:

  • Fibrillogenesis. We investigate how natural and synthetic polymers come together and assemble into a fibrous network. Inspired by how cells build their extracellular matrix, we develop experimental strategies to induce fibrillogenesis across multiple spatial scales (nano- to centi- meter). Based on the structure and composition of the self-assembling protein or polymer network of interest, we explore applications that can range from tissue engineering to textile design.
  • Bionics. Engineering at the biotic-abiotic interface by modifying the natural function and composition of the extracellular matrix will not only provide alternative substrates for wearable or implantable electronics that are flexible but also introduce new materials that are capable of chemically coupling to tissues and organs in vivo. We adapt additive manufacturing techniques to build customizable protein based materials. We are developing chemistries that will enable us to re-purpose protein binding domains towards these applications.
  • Bio-optics.  Cephalopods such as squid, octopus, and cuttlefish are capable of rapid (~100 msec) and adaptive changes in coloration by varying the local distribution of dermal pigments and proteins to reflect, absorb, and transmit light. We study the molecular mechanism that regulates this process, where we focus specifically on the role of their pigment-containing nanoparticles in absorbing and scattering light across the ultraviolet through short-wave infrared regions. We build materials inspired by the cephalopods designed to enhance these characteristics for wearable applications. We also dedicate time to optimizing and innovating methods to harness the pigments and proteins found in cephalopod tissue. More information specific to our squid dissections can be found here.