Editorial Cite This: Biochemistry 2018, 57, 1−8
pubs.acs.org/biochemistry
Introducing the “Future of Biochemistry” Special Issue
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cell death. We are particularly interested in the involvement of lipids in distinct membrane-related changes that take place during different forms of programmed cell death and how subtle differences in lipid structure affect their function. In addition to state-of-the-art analytical methods, we utilize chemical and molecular biology tools to elucidate the regulation and role of these fascinating biomolecules in cell biology.
n 1987, Nobel prize winner Arthur Kornberg wrote a particularly insightful commentary in Biochemistry entitled “The two cultures: chemistry and biology”.1 Arthur noted that “Increasingly, young professors in chemistry departments are pursuing problems of biologic significance.” The unique synergy between chemistry and biology has become increasingly apparent and multidimensional over the past 30 years and is certain to continue to grow and deepen as chemists and biologists set their sights on increasingly complex problems. I am proud to dedicate this month-long special issue to the Future of Biochemistry, and the early career scientists across the globe who are combining an ever diversifying set of skills and backgrounds to tackle problems of biochemical relevance. I am pleased to celebrate their work in this special issue and provide them with a focused forum to communicate their ideas, visions, and passions. Brief descriptions of the research programs of most of our Future of Biochemistry contributors are included below. Be on the lookout for Biochemistry papers from each of these very talented individuals! Best wishes for the holidays and New Year. Sincerely,
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YIMON AYE Assistant Professor and Milstein Faculty Fellow, Cornell University B.S./M.S. University of Oxford Ph.D. Harvard University Postdoc Massachusetts Institute of Technology The Aye lab strives to resolve unconventional signaling paradigms in the realms of electrophile signaling and genome regulation. The first program is ultimately aimed at translating the precision cysteome signaling code and how these chemical messages exert influence in biological decision making using worm, fish, and cultured cells as models. The second program interrogates natural and non-natural nucleotide ligand-driven novel check-point signaling mechanisms of importance in mammalian genome maintenance.
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Alanna Schepartz, Editor-in-Chief
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JEREMY BASKIN Assistant Professor and Nancy and Peter Meinig Family Investigator, Cornell University B.S. Massachusetts Institute of Technology Ph.D. University of California, Berkeley Postdoc Yale University Research in the Baskin lab sits at the interface of chemical biology, cell biology, and neurobiology of lipid biosynthesis and signaling. Current projects include both development of new chemical tools and hypothesis-driven cell biology efforts to elucidate biological functions of lipids and membranes in health and disease. We are developing novel bioorthogonal reporters to visualize and study specific sectors of the lipidome, including phosphatidic acid production by phospholipase D enzymes. In addition, we are studying the biology of inositolcontaining phospholipids (phosphoinositides), working to elucidate mechanisms controlling their synthesis at the plasma membrane and specific roles they play in the formation of the myelin sheath during nervous system development and following injury in demyelinating diseases such as multiple sclerosis.
NOZOMI ANDO Assistant Professor, Princeton University B.S. Massachusetts Institute of Technology M.S./Ph.D. Cornell University Postdoc Massachusetts Institute of Technology Going beyond the static pictures of macromolecules is the next frontier of structural enzymology. With this goal in mind, my laboratory works at the interface of physical and biological chemistry to develop nonconventional X-ray scattering and diffraction methods that provide information about protein motion. Enzymes that utilize metal-containing cofactors are of particular interest to us, both for the fascinating reactions that they are able to catalyze and for their physical properties. By utilizing new physical methods, we are interested in determining correlated motions that underlie protein allostery and conformational changes that allow dynamic enzymes to tune their activities and perform sequential reactions in the correct order.
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G. EKIN ATILLA-GOKCUMEN J. Solo Assistant Professor, University of Buffalo B.A. Koc University Ph.D. University of Pennsylvania Postdoc Harvard Medical School/Dana Farber Cancer Institute My lab consists of a group of scientists interested in lipids and how these molecules are involved in different cellular processes. Using untargeted lipidomics as an unbiased discovery tool, we study how the compositional regulation and spatial regulation of lipids contribute to senescence and © 2018 American Chemical Society
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ANDREW BEHARRY Assistant Professor, University of Toronto B.Sc. York University Ph.D. University of Toronto Special Issue: Future of Biochemistry Published: January 9, 2018 1
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Postdoc Stanford University The standard care of cancer therapy consists of diagnosis and surgery, followed by chemotherapy and/or radiation therapy. Although this regimen works well with some cancers, most cancers respond poorly to these treatments. Consequently, only marginal improvements in patient survival rates are observed. My research program is dedicated to solving this problem by developing new diagnostic tools and treatment platforms that work alongside or replace conventional cancer therapies. Specifically, our current focus is on chemosensors for diagnosis/drug screening and on drugs that can be utilized for fluorescence-guided surgery/photodynamic therapy.
the context of mammalian cells. To this end, we are developing new aminoacyl-tRNA synthetase (aaRS)/tRNA pairs, orthogonal in eukaryotic cells, which can be engineered to charge previously inaccessible ncAAs. We are also expanding the scope of this powerful technology by improving the performance of these heterologous aaRS/tRNA pairs in mammalian cells through rational engineering as well as directed evolution and by enabling site-specific incorporation of multiple distinct ncAAs per polypeptide.
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GANG CHEN Assistant Professor, Nanyang Technological University B.Sc. University of Science and Technology of China Ph.D. University of Rochester Postdoc The Scripps Research Institute The Chen research group employs conventional and cuttingedge biophysical and biochemical techniques to better understand the structures and the physicochemical properties of RNAs, proteins, and RNA−protein complexes. For example, we characterize RNA folding dynamics and the effects of sequence and environmental factors such as proton and protein binding by single-molecule mechanical unfolding methods using analytical optical tweezers. We aim to develop novel biological tools and therapeutic ligands to facilitate precise control of biological functions of important biomolecules related to neurodegenerative diseases, cancers, and bacterial and viral infections. For example, we have been developing chemically modified peptide nucleic acids (PNAs) that show sequence-specific and selective recognition of double-stranded RNAs over single-stranded RNAs and double-stranded DNAs. To approach the challenging goals, we have assembled a collaborative team with expertise in molecular biophysics, structural biology, computation, chemical synthesis, cell biology, and animal model studies.
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MICHAEL BOYCE Assistant Professor, Duke University B.A. Harvard College Ph.D. Harvard Medical School Postdoc University of California, Berkeley My lab studies mammalian cell signaling through protein glycosylation. Glycosylation is the most abundant posttranslational modification in nature, and as a sugar-based modification, it lies at the nexus of cell signaling and cell metabolism. However, because glycosylation is a dynamic, nontemplated, and chemically complex process, it can be challenging to study with conventional biological techniques alone. We use a range of biochemical, cell, chemical, and structural biology methods to dissect the role of mammalian protein glycosylation. Our current work focuses on two specific areas. First, we aim to understand how dynamic signaling by O-linked β-N-acetylglucosamine on intracellular proteins senses and regulates cell physiology. Second, we are dissecting the cell- and systems-level regulation of nucleotide−sugar metabolites in health and disease.
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LOUISE CHARKOUDIAN Assistant Professor, Haverford College B.S. Haverford College Ph.D. Duke University Postdoc Stanford University Research in our lab focuses on understanding how nature evolved the ability to make structurally complex molecules and how humans can apply this knowledge to create sustainable routes to new chemical diversity. We employ tools at the interface of chemistry, biology, and physics to study the transient protein−protein interactions involved in the biosynthesis of polyketides, fatty acids, and nonribosomal peptides. We also leverage computational approaches to identify target biosynthetic gene clusters to mine for new chemical and enzymatic diversity. Work in our lab is driven by undergraduate student researchers, and we are passionate about integrating original research opportunities into the undergraduate classroom setting.
PENG CHEN Professor of Chemical Biology, Peking University B.Sc. Peking University Ph.D. The University of Chicago Prof. Chen’s research direction focuses on developing and applying novel chemistry tools for investigating protein-based interactions and activities in living systems. He has developed a versatile protein chemistry toolkit to capture, manipulate, and label signaling proteins and protein−protein interactions inside living cells. In particular, his lab is one of the earliest laboratories that started to develop bioorthogonal cleavage reactions that are beyond the traditional ligation-centered bioorthogonal chemistry. Such reactions have now found broad applications, ranging from gain-of-function study of intracellular enzymes (e.g., kinases) to the direct manipulation of intact cells (e.g., immune cells) under physiological settings. His lab also developed a series of genetically encoded, highly efficient photo-cross-linkers for trapping protein−protein interactions and elucidated the mechanism underlying bacterial acid resistance and antibiotic tolerance.
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ABHISHEK CHATTERJEE Assistant Professor, Boston College B.Sc. University of Calcutta M.S. Indian Institute of Technology Kharagpur Ph.D. Cornell University Our group is interested in genetically encoding enabling noncanonical amino acids (ncAAs) in eukaryotes and their use in probing and engineering eukaryotic biology, particularly in
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CELESTINE CHI
Assistant Professor, Uppsala University M.Sc. Linkoeping University Ph.D. Uppsala University Postdoc ETH Zürich 2
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discovery method (rational design to unbiased evolution). In all cases, our ultimate goal is to leverage new chemical and molecular technologies to better understand and treat human disease. One focal point in the lab at this time is understanding how dynamic lipid modifications on the mammalian proteome are regulated and control cellular physiology. Another focal point in the lab is developing new biosensing technologies for synthetic biology applications, which in turn is leading to new methods for measuring, controlling, and evolving biological systems.
We want to understand the role played by the outer membrane (OM) in the development of antibiotic resistance in Gram-negative bacteria. Most antibiotics are targets for intracellular processes. However, they must be able to pass through the OM protective coating. Antibiotics may either penetrate these coatings through a lipid-mediated mechanism or diffuse through porin proteins. Drug resistance to antibiotics most often is associated with modification of the lipid−protein composition of the OM. The mechanistic and molecular basis of how the OM components interact with antibiotics is poorly understood. We want to study at the molecular level by nuclear magnetic resonance spectroscopy the mechanism of antibiotic transition across the OM. These results will be fundamental for the development of new antibiotics.
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MIKEL GARCIA-MARCOS Assistant Professor, Boston University B.Sc., Ph.D. University of the Basque Country Postdoc University of California, San Diego We investigate signal transduction mechanisms with the ultimate goal of elucidating the molecular basis of human diseases and developing novel therapeutic approaches. Our main interest is in heterotrimeric G proteins, which are molecular switches that relay extracellular signals. Heterotrimeric G proteins are primarily activated by G proteincoupled receptors (GPCRs) located at the plasma membrane. However, our lab focuses on a group of cytoplasmic factors that mimic the action of GPCRs by directly activating heterotrimeric G proteins. We are exploring this unconventional aspect of G protein signaling in the context of cancer, embryonic development, and neurotransmission by using a multidisciplinary approach that encompasses in vitro biochemistry, cell biology, and different model organisms to elucidate functional consequences in vivo.
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JASON CRAWFORD Associate Professor, Yale University M.D., Ph.D. Johns Hopkins University Using an interdisciplinary blend of metabolomics, protein biochemistry, natural product chemistry, and microbiology, the Crawford lab decodes novel metabolic pathways in bacteria associated with humans and other animals. Many of the bacterial metabolites that evolved to regulate host biology are potent and are produced in very low abundances. Consequently, sourcing for a majority of novel metabolites at sufficient levels for rigorous structural and functional characterizations represents a major challenge in the field. To access this underlying metabolic chemistry from complex microbial consortia, the lab employs a variety of reductionist approaches to identify key bacterial metabolic pathways that regulate targeted host phenotypic outcomes. Some of our projects are in collaboration with immunologists, which provides complementary vantage points to place the metabolic chemistry into broader biological contexts.
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MING HAMMOND Assistant Professor, University of California, Berkeley B.S. California Institute of Technology Ph.D. University of California, Berkeley My lab has a dual focus on nucleic acids as engineerable biosensors and as novel signaling agents. We are one of the first groups to develop fluorescent biosensors made of RNA for live cell imaging of otherwise “invisible” chemical signals. We aim to continue leading the development of novel biosensors to broadly enable high-throughput screening, microscopy, flow cytometry, and other bioanalytical methods to study enzyme activity, metabolism, and signaling in cells, tissues, and organisms. Our current major biological focus is understanding how bacterial and immune cells make decisions. Via the study of key cyclic dinucleotide signaling pathways that control the autonomous behavior of these cell types, our long-term goals are to provide new ways to combat antibiotic-resistant bacteria and to enhance the effectiveness of cancer immunotherapies.
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EMILY DERBYSHIRE Assistant Professor, Duke University B.S. Trinity College Ph.D. University of California, Berkeley The Derbyshire lab uses chemical approaches to explore the biology of malaria with the goal of advancing therapeutic design. We develop and apply small molecule probes to study infectious disease agents and their interactions with hosts, with a current focus on the malaria parasite that infects liver and blood cells. Our interdisciplinary research program integrates genomics and chemical biology to elucidate host processes critical for malaria parasite infection. We also employ enzymology, proteomics, and metabolomics to characterize parasite signaling pathways. Through our studies, we aim to discover parasite and host factors that are essential to malaria to facilitate drug development.
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KU-LUNG HSU Assistant Professor, University of Virginia B.S. Louisiana State University Ph.D. The University of Texas at Austin Postdoc The Scripps Research Institute Dr. Hsu’s research program is focused on developing chemical methods and probes to address fundamental challenges associated with studying regulation of metabolism and signaling in vivo. Current efforts are focused on discovery of new lipid metabolic targets for chronic inflammation and immuno-oncology. Members of his group receive crossdisciplinary training in chemical biology, mass spectrometry,
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BRYAN DICKINSON Assistant Professor, The University of Chicago B.S. University of Maryland Ph.D. University of California, Berkeley Postdoc Harvard University Our group works in complementary areas of basic and applied biology with the overarching theme being the creation of functional molecules that lead to biological breakthroughs. The functional molecules we are creating vary in terms of size (small molecules to proteins to engineered organisms) and 3
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medicinal chemistry, and in vivo pharmacology. Dr. Hsu’s research has been recognized by several awards, including the highly competitive National Institutes of Health K99/R00 Pathway to Independence Award and the Department of Defense CDMRP Career Development Award.
infections and identify new antimicrobial targets for difficultto-treat pathogens.
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WEIKAI LI Assistant Professor, Washington University School of Medicine in St. Louis. B.Sc. East China University of Science and Technology M.Sc. University of Tennessee Knoxville Ph.D. Yale University My lab studies the structural biology of membrane proteins that are important in hematology and cardiovascular biology. Our current research is focused on intramembrane enzymes involved in the vitamin K metabolism and membrane transporters controlling iron homeostasis. We have determined crystal structures of vitamin K epoxide reductase, the target of most commonly used anticoagulants, and structures of UbiA superfamily prenyltransferases essential to vascular homeostasis, electron transport, and antioxidation. The structural insights have allowed us to investigate deeply the biochemical property and cellular function of these proteins. To meet the challenge of membrane protein studies, we have developed new crystallographic methods and innovated applications of mass spectrometry in living cells. With this integrative approach, my lab aims to drive the structural biology to a new level as we focus on membrane proteins in cardiovascular medicine.
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RALPH KLEINER Assistant Professor, Princeton University A.B. Princeton University Ph.D. Harvard University Postdoc The Rockefeller University RNA is a central molecule in biology, and its function can be regulated by chemical modifications. While modifications on stable, long-lived RNA species such as tRNA have been known for decades, we are only now beginning to appreciate that more transient molecules, such as mRNA, are also subject to diverse modifications. My lab is interested in how chemical modifications on RNA affect function. In particular, we are investigating how “epitranscriptomic” modifications, which occur on mRNA and can regulate gene expression, effect protein−RNA interactions in the cell. Toward this goal, we apply diverse approaches integrating chemistry and biology, including the synthesis of chemical probes, chemical proteomics, and cellular imaging techniques.
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KYLE LANCASTER Assistant Professor, Cornell University B.A. Pomona College Ph.D. California Institute of Technology Postdoc Cornell University The Lancaster group employs a diverse array of physical and computational methods to establish electronic structure− function relationships in synthetic and biological transition metal catalysts. Studies in the latter arena focus on understanding metalloenzyme-mediated transformations during nitrification, the oxidative steps of the nitrogen cycle wherein certain organisms use ammonia as their sole cellular fuel. Ongoing research attempts to answer how nitric oxide serves as a central “currency” among consortia of ammonia-oxidizing microbes, how energy transduction is balanced with management of toxic metabolites, including hydroxylamine, and how nature selectively oxidizes ammonia to hydroxylamine.
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THOMAS MAKRIS
Assistant Professor, University of South Carolina B.A. University of Pennsylvania Ph.D. University of Illinois at Urbana-Champaign Postdoc University of Minnesota My independent research program focuses on enzymes that are involved in the synthesis of products of industrial and biomedical importance. This includes the characterization of enzymes involved in transforming metabolites from the fatty acid synthesis pathway into hydrocarbons that can serve as fuels and important chemical building blocks. Another area of investigation is understanding enzymes that are important for the biosynthesis of antibiotics that are important mainstays in the clinic.
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STEVE MANSOORABADI Assistant Professor, Auburn University B.S., P.B.C. University of WisconsinMilwaukee Ph.D. University of WisconsinMadison Postdoc The University of Texas at Austin Dinoflagellates make up an important group of eukaryotic microorganisms. Certain species produce potent neurotoxins and are responsible for red tides, while others are capable of both photosynthesis and bioluminescence. A key event in the circadian regulation of dinoflagellates is the degradation of chlorophyll to the open-chain tetrapyrrole dinoflagellate luciferin (LH2), which is the light-emitting substrate of the pH-regulated dinoflagellate luciferase (LCF) enzyme. The catabolic process leading to LH2 is unknown, and its elucidation may lead to the development of specific pathway inhibitors that may find application in the remediation of coastal seawaters. These studies will also help facilitate the use of LCF as a reporter enzyme and cellular imaging agent. In addition, LCF provides an excellent model system for the study
BO LI Assistant Professor, University of North Carolina at Chapel Hill B.S. Peking University Ph.D. University of Illinois at Urbana-Champaign Postdoc Harvard Medical School My laboratory studies antibiotics and other bioactive bacterial metabolites with the goal of combatting infectious disease. First, we investigate the mode of action of antibiotics to identify useful antimicrobial mechanisms. We study a unique class called dithiolopyrrolones that chelate metal ions in the cell. We are also discovering and designing hybrids and cocktails of antibiotics as novel antimicrobials. Second, we decipher the biosynthetic chemistry of antibiotics to uncover new enzymatic transformations and accelerate the discovery of new antibiotics. Third, we mine bacterial genomes to identify bacterium-derived metabolites that mediate bacterium− bacterium and bacterium−host interactions. Our purpose is to understand the multifaceted roles of metabolites in 4
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grave as we seek to understand LPL folding in the endoplasmic reticulum, its secretion, and its regulation once it reaches the blood. We are especially interested in understanding the molecular basis for the interaction of LPL with partner proteins and the mechanisms by which LPL is regulated.
of both pH-dependent enzyme dynamics and biological mechanisms of chemiluminescence.
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EVAN MILLER Assistant Professor, University of California, Berkeley B.S., B.A. Point Loma Nazarene University Ph.D. University of California, Berkeley My lab operates at the interface of organic chemistry, chemical biology, and neuroscience. We use the principles of molecular design to invent, build, and apply new chemical tools for understanding fundamental cell physiology. In particular, we are interested in how cells, tissues, and organs use ionic fluxes and the resulting changes in membrane potential to drive a host of important processes.
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SABINE PETRY Assistant Professor, Princeton University M.Sc. Goethe Universität and Max Planck Institute of Biophysics Ph.D. MRC Laboratory of Molecular Biology/University of Cambridge Postdoc University of California, San Francisco The mission of my lab is to understand how cells acquire their shape, position organelles, move materials, and segregate chromosomes during cell division. These features are organized by the microtubule (MT) cytoskeleton, which resembles the skeletal system that supports our human body. Its biological function relies on the precise arrangement of MTs in the cell. To achieve this organization, MTs are generated at defined locations and then organized by proteins, which sever, polymerize, shrink, bundle, anchor, or move MTs. We want to understand these functionalities mechanistically and study them by combining methods of cell biology, biochemistry, biophysics, structural biology, and engineering. This will ultimately reveal how the MT cytoskeleton builds structures to support essential functions of the cell and enable us to address malfunction of the MT cytoskeleton, which lie at the heart of many diseases involving cell proliferation and cancer.
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MANUAL MÜ LLER Sir Henry Dale Fellow, King’s College London M.Sc., Ph.D. ETH Zürich Postdoc The Rockefeller University and Princeton University My lab is interested in understanding how post-translational modifications control proteins. We are especially interested in how modifications of the polypeptide backbone contribute to cellular signaling and endow proteins with new properties. To study these processes, we develop and apply protein chemistry and engineering methods, including protein semisynthesis and directed evolution. These tools enable us to precisely manipulate the chemical makeup of proteins and directly measure the functional consequences of post-translational modifications in biochemically controlled settings.
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ANDRÉ NADLER Research Group Leader, Max Planck Institute of Molecular Cell Biology and Genetics Diploma, Ph.D. Georg-August Universität Göttingen Postdoc European Molecular Biology Laboratory My lab is particularly interested in quantitatively analyzing membrane-related processes and combines organic chemistry, biochemistry, and cell biology in an interdisciplinary setting. We are trying to understand why there are so many molecular distinct lipid species, what their cellular roles, are and how their distribution in the membrane influences cellular signaling cascades. We believe that quantitative lipid biochemistry in living cells will be required to address these questions. Consequently, we focus on developing improved lipid biosensors and caged and photo-cross-linkable lipids both for modulating intracellular lipid pools with high temporal and spatial resolution and for screening for protein−lipid interactions. Ultimately, these chemical biology tool sets will enable measurement of KD values of lipid−protein interactions and lipid dynamics in the membranes of living cells.
SRIVATSAN RAMAN Assistant Professor, University of WisconsinMadison Ph.D. University of Washington Postdoc Harvard Medical School Wyss Technology Development Fellow, Wyss Institute, Harvard University My laboratory uses principles of systems and synthetic biology to understand and design allosteric proteins. Our research integrates computational protein modeling (Rosetta) and highly multiplexed experiments to study ligand-inducible allosteric transcription factors in prokaryotes and eukaryotes. We employ deep mutational scanning to elucidate the underlying functional landscape of allosteric transcription factors by interrogating the role of individual amino acids. Because allosteric transcription factors are widely used as biosensors, we design these proteins toward new ligand and DNA specificities to expand the suite of available biosensors for medical, environmental, and bioenergy applications.
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HANS RENATA Assistant Professor, The Scripps Research Institute B.A. Columbia University Ph.D. The Scripps Research Institute Postdoc California Institute of Technology The Renata lab is interested in developing enzymatic solutions for traditionally challenging organic reactions and applying these biotransformations in the chemoenzymatic synthesis of bioactive natural products and their analogues. Special attention is given to oxygenases that display novel reactivities in the realm of C−H functionalization chemistry. By mining the inherent sequence diversity of natural oxygenases and combining it with contemporary methods of
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SASKIA NEHER Assistant Professor, University of North Carolina at Chapel Hill B.S. University of Oregon Ph.D. Massachusetts Institute of Technology Postdoc University of California, San Diego Lipoprotein lipase (LPL) is an enzyme present in the blood that functions to regulate plasma triglyceride levels. Because elevated plasma triglycerides are associated with an increased risk of heart disease, my lab aims to understand factors that affect LPL levels and activity. We study LPL from cradle to 5
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proteins, protein engineering experiments to evolve new function, and cell biological and genetic studies to understand how this machinery functions in the context of the cell. In addition, the lab develops enabling tools in the genome editing space to facilitate these experiments.
enzyme engineering, we aim to generate a new biocatalytic toolkit to expedite synthetic access to therapeutically relevant small molecules.
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ALEXANDER RUTHENBURG Associate Professor, The University of Chicago B.A. Carleton College Ph.D. Harvard University Postdoc The Rockefeller University My research program spans several traditional disciplines (discovery biochemistry, chemical biology, biophysics, technology development, quantitative genomics, and cell biology) with the goal of developing a fundamental mechanistic understanding of epigenetic information systems through three main avenues. (1) We have pioneered the use of barcoded semisynthetic nucleosomal calibrants to enable absolute quantification of histone marks and variants in chromatin immunoprecipitation experiments. This method circumvents serious pitfalls in ChIP and probes finer scale chromatin features in cells than previously possible, powerfully enabling new discoveries and resolving long-standing questions in the field. (2) A second major effort in the lab is the biochemical discovery of new epigenetic pathways, centered on orphaned histone marks and DNA modifications that have resisted elucidation of specific binding-driven pathways. (3) My lab has discovered a new class of noncoding RNA molecules, which display potent enhancer activity and are defined by tight attachment at their site of transcription. We have recently developed compelling evidence of their generality and begun defining their molecular mechanisms.
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SARAH SLAVOFF Assistant Professor, Yale University B.S. University of Maryland Ph.D. Massachusetts Institute of Technology Postdoc Harvard University The Slavoff research group works at the interface of chemistry and biology to develop new technologies that allow us to rethink how genomes work. Specifically, we are interested in the discovery and characterization of functional small open reading frames in “noncoding” RNA, (chemo)proteomic profiling of noncanonical protein translation initiation, and mechanistic study of the spatiotemporal regulation of mRNA decay in eukaryotic cells. Examples include our recent discoveries of novel Escherichia coli cold shock and heat shock proteins, as well as a human microprotein that interacts with the mRNA decapping complex and cellular RNA−protein granules known as P-bodies.
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ALEXANDER SOBOLEVSKY Associate Professor, Columbia University M.S., Ph.D. Moscow Institute of Physics and Technology My lab studies the structure and function of ion channels, including ionotropic glutamate receptors and transient receptor potential channels, using different biophysical and biochemical techniques, such as X-ray crystallography, cryoelectron microscopy, kinetic modeling, and electrophysiology. We are interested in understanding the mechanism of gating that leads to opening or closure of the ion channel pore for the flow of permeant ions. We explore the molecular composition of the ion channel gates as well as conformational changes in the ion channel protein associated with gating. We also study molecular mechanisms of ion channel assembly, interaction with auxiliary subunits, regulation by competitive antagonists, channel blockers, and allosteric modulators. A better understanding of these mechanisms will help to bolster our knowledge of ion channel functional architecture and drug design.
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SARVENAZ SARABIPOUR Postdoctoral Fellow, Johns Hopkins University B.Sc. University of Sydney M.Sc. Université de Sherbrooke M.S.E., Ph.D. Johns Hopkins University My research focuses on computational analysis of the endothelial receptors and corresponding signaling networks that regulate angiogenesis. We build in silico multiscale models to simulate and understand the effect of growth factors and therapeutics on human physiology and pathophysiology. I study vascular endothelial receptor (VEGFR) regulation of angiogenesis, complicated by the ischemic conditions in peripheral artery disease and diabetes. The models enable us to design specific interventions, targeting VEGF signaling, that promote angiogenesis. This can be achieved only by building computational models that simulate cell and tissue contexts. In our contribution, we describe how mathematical modeling coupled with biochemical experiments has unraveled the intricate signaling dynamics of the NF-κB transcription factor system in response to extracellular binding factors, pharmaceuticals, and other therapies.
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CHUN TANG Distinguished Investigator, Wuhan Institute of Physics B.S. Zhejiang University Ph.D. University of Maryland Dr. Tang and his group are interested in the dynamic properties of proteins and their complexes, and how the dynamics enable protein functions. In particular, they are interested in how the constituent domains and subunits in proteins and protein complexes are spatially rearranged upon post-translational modifications and environmental cues. Their work led to the elucidation of the recognition mechanism between K63-linked polyubiquitin and its target proteins. Dr. Tang is one of the pioneers of using paramagnetic nuclear magnetic resonance (NMR) to visualize protein dynamics. His group is now developing computational methods to integrate NMR and other biophysical and biochemical data for better characterization of protein ensemble structures.
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DAVID SAVAGE Associate Professor, University of California, Berkeley B.A. Gustavus Adolphus College Ph.D. University of California, San Francisco Postdoc Harvard Medical School Research in the Savage lab focuses on developing integrative tools for studying protein function. Their model system of interest is photosynthetic carbon dioxide assimilation. Current projects include mechanistic studies of CO2-assimilating 6
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KENNETH WESTOVER Assistant Professor, University of Texas Southwestern Medical Center B.S. Brigham Young University Ph.D., M.D. Stanford University The Westover lab is focused on developing new, targeted cancer therapies. We focus on a range of biological targets and collaborate with many other laboratories to expedite our mission to alleviate the burden of cancer for those who suffer. Our general philosophy is that basic research will enable important discoveries that lead to revolutionary cancer treatments. In particular, we believe that structural studies of biological macromolecules are crucial for progress.
Principal Investigator, University of Edinburgh B.Sc., M.Sc., Ph.D. University of Barcelona Optical imaging has revolutionized our understanding of how biological systems behave at a molecular level. In 2012, I started my independent career in Edinburgh with the vision of translating chemical fluorophores to the clinic. In my group, we develop activatable fluorophores to image processes associated with inflammation and cancer with the aim of interrogating biology in real time as well as providing better tools for diagnosing and treating disease. We create activatable fluorophores using a multidisciplinary approach that involves organic and peptide chemistry, spectroscopy, biology, and imaging. Our imaging probes emit a fluorescent signal only after they interact with their target molecules, which allows them to be used in small doses, reducing any potential adverse effects and facilitating their translation to the clinic.
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CHRISTINA WOO Assistant Professor, Harvard University B.A. Wellesley College Ph.D. Yale University The Woo lab studies how small molecules influence protein function using a combination of organic chemistry, chemical biology, and mass spectrometry. Small molecules are one of the primary means of regulating biology by both native cellular processes (e.g., post-translational modifications) and humans (e.g., small molecule therapeutics). My lab is involved in developing general approaches to directly characterize and engineer these interactions. We are creating chemical technologies that enable global mapping of small molecule binding sites to proteins. In parallel, we are developing new tools to probe and engineer cellular pathways that rely on small molecule signaling. We will apply these methods to bioactive small molecules to gain insight into the biological terrain under a small molecule’s purview that is overlooked with existing technologies.
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CHU WANG Assistant Professor, Peking University B.S. University of Science and Technology of China Ph.D. University of Washington Postdoc University of Washington, The Scripps Research Institute Our research group aims to develop and apply multidisciplinary tools in chemoproteomics, biochemistry, bioinformatics, and computational structure biology to uncover targets of bioactive molecules (natural products, endogenous metabolites, clinical drugs, etc.) as well as sites of posttranslational modification in proteomes. We also study the functional impact of these molecular interactions and modifications on cellular metabolism and signal transductions and computationally model and design key interactions to perturb and/or regulate these functional pathways. These studies have great potential to provide penetrating mechanistic insights into the molecular basis of numerous diseases functionally linked to oxidative stress, including inflammation, cancer, and metabolic disorders, as well as to integrate and streamline efforts in inhibitor discovery, drug design, and the functional annotation of uncharacterized enzymes in the postgenomic era.
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KENICHI YOKOYAMA Assistant Professor, Duke University Medical Center B.S., Ph.D. Tokyo Institute of Technology Postdoc Massachusetts Institute of Technology My group has been interested in the functions and mechanisms of enzymes related to the cofactor and natural product biosynthesis and mode of action. One area of our interests is the radical SAM (S-adenosyl-L-methionine) enzymes responsible for the construction of the unique carbon skeletons during natural product and cofactor biosynthesis. Elucidation of their functions is important for understanding the biosynthetic pathways and the catalytic scope of radical SAM enzymes. Another area of interest is the group of enzymes responsible for fungal cell wall biosynthesis. These enzymes are proven targets of antifungal natural products. Together with the biosynthetic studies, we aim to provide intellectual foundations for the development of novel therapeutics against life-threatening fungal infectious diseases.
TIMOTHY WENCEWICZ
Assistant Professor, Washington University in St. Louis B.S. Southeast Missouri State University Ph.D. University of Notre Dame Our laboratory is focused on elucidating molecular mechanisms of antibiotic action, biosynthesis, and resistance to spark innovation for antibacterial drug discovery. We look to nature’s chemical inventory for inspiration to find new antibiotic scaffolds that act on new biological targets and evade established clinical resistance mechanisms. We have four major research efforts in my laboratory: (1) natural product biosynthesis, (2) emerging antibiotic resistance enzymes, (3) siderophore-mediated iron acquisition in bacteria, and (4) mechanism-based enzyme inhibitors. Our approach is highly interdisciplinary and molecule-centered. We leverage our skills in synthetic organic chemistry, mechanistic enzymology, and microbiology to answer challenging scientific questions of broad interest to the infectious disease community.
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HIDEAKI YOSHIMURA Assistant Professor, The University of Tokyo B.Eng., M.Eng. Kyoto University Ph.D. The Graduate University for Advanced Studies, Japan My research interests are development of fluorescent probes to visualize real-time motions of target molecules in living cells and revealing the molecular mechanisms of physiological events based on molecular motions. The major targets for visualization are RNA and signaling proteins. Using the probes 7
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and homemade TIRF microscopes, I perform single-molecule imaging in living cells and analyze the diffusion motions of the target molecules. On the basis of the observed single-molecule motions, nonhomogeneous and transient motion changes, in which the molecule is truly functioning, are detected and analyzed. On the basis of these analyses, I investigate the molecular mechanisms of living systems.
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TAN ZHONGPING Assistant Professor, University of Colorado, Boulder B.S., M.S. Peking University M.A., M.Phil., Ph.D. Columbia University Postdoc Memorial Sloan Kettering Cancer Center Our general research interests are in the field of glycoscience. We aim to develop a detailed, quantitative understanding of the roles of glycans in fundamental biological processes. Our research is built on a powerful platform of chemical synthesis technologies optimized for efficient and reliable production of structurally defined glycans, glycoproteins, and other glycoconjugates. Taking advantage of the highly flexible and precise nature of chemical synthesis, we have successfully applied a systematic, library-based approach to analyze large collections of synthetic glycoforms and significantly improved our knowledge of protein O-glycosylation. Our focus now is leveraging the unique power of this chemical glycobiology method to answer increasingly complex biological questions, including the structure−function relationships of functional glycans and large glycoproteins and the composition−function relationships of glycoform mixtures. Alanna Schepartz* Department of Chemistry, Yale University, 225 Prospect Street, New Haven, Connecticut 06520, United States
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AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. ORCID
Alanna Schepartz: 0000-0003-2127-3932 Notes
Views expressed in this editorial are those of the author and not necessarily the views of the ACS.
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REFERENCES
(1) Kornberg, A. (1987) The two cultures: chemistry and biology. Biochemistry 26, 6888−6891.
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DOI: 10.1021/acs.biochem.7b01259 Biochemistry 2018, 57, 1−8
