Introducing “Future of Biochemistry: The International Issue

3 days ago - Department of Chemistry, Yale University , 225 Prospect Street, New Haven , Connecticut 06520 , United States. Biochemistry , 2019, 58 (1...
1 downloads 0 Views 279KB Size
Editorial Cite This: Biochemistry 2019, 58, 1−6

pubs.acs.org/biochemistry

Introducing “Future of Biochemistry: The International Issue”

Biochemistry 2019.58:1-6. Downloaded from pubs.acs.org by 91.204.15.57 on 01/08/19. For personal use only.

W

Ph.D. The Scripps Research Institute Postdoc Albert Einstein College of Medicine Eukaryotic cells are highly compartmentalized and this organization plays a key role in regulating gene expression. The molecular mechanisms that control the spatial and temporal regulation of gene expression, however, are poorly understood. Research in our group focuses on understanding the cytoplasmic lives of mRNAs. To this end, we engineer multicolor fluorescent RNA biosensors that allow individual translation and degradation events of single mRNAs to be quantified in real-time in living cells. We also complement our in vivo single-molecule imaging studies with in vitro biochemical and structural characterization of RNA−protein complexes in order to understand how these macromolecules interact and function within their cellular context. Our current focus is on understanding the spatiotemporal regulation of gene expression during the integrated stress response.

elcome to the Future of Biochemistry: The International Issue. I am excited to begin the 58th year of Biochemistry by introducing a second set of fantastic early career biological chemists. I encourage you to peruse their biographies and research programs and in doing so recognize how many are tackling problems that transcend traditional field boundaries and challenges that seemed impossible only decades ago. Many of our featured scientists trained in multiple laboratories across the globe, bringing new and innovative ideas with them wherever they went. The field of biochemistry has a global future, and the journal Biochemistry is proud to share that future with you.



TOBIAS BECK Research Group Leader, RWTH Aachen University, Germany Diploma, Ph.D. Georg-August Universität Göttingen Postdoc ETH Zürich My research group is working on the construction of highly structured nanomaterials based on proteins and inorganic nanoparticles. Toward this goal, my group combines protein design and protein crystallography with nanoparticle synthesis and functionalization. With my group, I have recently introduced a novel method for the construction of well-defined biohybrid materials. Protein containers, engineered with an opposite surface charge, are used as an atomically precise ligand shell for the assembly of inorganic nanoparticles. The assembly of protein−nanoparticle composites yields highly ordered nanoparticle superlattices with unprecedented precision and lateral sizes of the binary superlattices. Our materials could pave the way toward renewable materials based on protein building blocks, with an additional functionality from inorganic components.



SHU-SIN CHNG Associate Professor, National University of Singapore, Singapore B.Sc. (Hons), National University of Singapore Ph.D. Harvard University Postdoc Harvard Medical School The Chng research group focuses on understanding how biological membranes are assembled in living cells, in particular, using bacterial outer membranes as interesting models. We study both Gram-negative bacteria and mycobacteria, which have separately evolved to assemble a second (outer) membrane in their cellular envelopes. These bacteria have to transport proteins and lipids and build their outer membranes at a distance away from the cytoplasmic membrane. Using chemical and biological approaches, we tackle problems in bacterial lipid trafficking and outer membrane assembly. The outer membrane serves as a formidable permeability barrier against toxic substances, in part rendering Gram-negative bacteria and mycobacteria intrinsically resistant to many clinically relevant antibiotics. Our work will eventually help identify novel targets in these bacteria and contribute to future antibiotic discovery efforts.



JENNIFER BRIDWELL-RABB Assistant Professor of Chemistry, University of Michigan, United States B.S. Central Michigan University Ph.D. Texas A&M University Postdoc Massachusetts Institute of Technology Microorganisms inhabit nearly every habitat on Earth and play fundamental roles in shaping our health and the environment. My research program seeks to investigate how microorganisms adapt their lifestyles and metabolism to factors such as light and molecular oxygen. We use a combination of X-ray crystallography, enzymology, and spectroscopy to understand how metalloenzymes build and customize lightabsorbing pigments, how metalloproteins react productively or destructively with oxygen, and how organisms sense environmental signals in the form of light, oxygen, and redox potential.



DANNY CHOU Assistant Professor, University of Utah, United States B.S., National Taiwan University Ph.D., Harvard University Postdoc, Massachusetts Institute of Technology My lab focuses on using protein engineering to create new peptide or protein derivatives to explore cell biology and develop therapeutics to treat human diseases. Our lab takes a huge effort to tackle type 1 diabetes (T1D), an autoimmune disease in which the pancreas stops producing insulin, a



JEFFREY CHAO Group Leader, Friedrich Miescher Institute for Biomedical Research, Switzerland B.A. Pomona College © 2019 American Chemical Society

Special Issue: Future of Biochemistry: The International Issue Published: January 8, 2019 1

DOI: 10.1021/acs.biochem.8b01293 Biochemistry 2019, 58, 1−6

Biochemistry

Editorial

Research in the D’Arcy group defines the relationship between structure, dynamics, and function for a diverse array of protein complexes. We aim to connect high-resolution static images of protein complexes to their movements in an aqueous environment. We want to understand how these movements play a role in either catalysis or binding events. We employ biochemical, biophysical, and structural approaches and have expertise in hydrogen−deuterium exchange coupled to mass spectrometry and X-ray crystallography. We are particularly interested in chromatin dynamics and macromolecular complexes involved in transcription, such as those containing histone chaperones and/or coactivators. Our article presents the crystal structure of a Nap-family histone chaperone from C. elegans and characterizes its binding to histones. It provides insight into how chaperones regulate nucleosome assembly and disassembly.

hormone that enables glucose uptake from blood. By developing novel insulin analogs, we hope to maintain normal blood glucose levels for people with type 1 diabetes. This manuscript to create a library of insulin-like peptides on yeast surface is one of our first steps toward identifying novel chemical probes to study insulin signaling as well as discovering new therapeutic lead molecules for tackling diabetes. This powerful method can greatly facilitate the discovery of new functional insulin molecules.



AMIT CHOUDHARY Assistant Professor of Medicine, Harvard Medical School, Broad Institute of MIT and Harvard, Brigham and Women’s Hospital, Unites States M.S. Indian Institute of Science, Bangalore Ph.D. University of Wisconsin−Madison Junior Fellow, Society of Fellows, Harvard University Our laboratory aspires to propel the development of therapeutics for diseases of poverty, including diabetes and malaria. We study exceptional organisms that survive conditions considered pathological to humans. For example, we study how binge-eating snakes, whose single meal contains more than 50 000 calories, survive the nutrient overload without becoming diabetic. In another area of research in our laboratory, we leverage chemistry to develop broadly applicable genome editing and CRISPR-based technologies that have the potential to impact multiple disease areas. Using such technologies, we are correcting disease-causing mutations, engineering insulin-producing beta cells that can evade the immune system in type 1 diabetes, and developing methods to efficiently immunize mosquitoes so they will not carry various deadly disease-carrying pathogens.



YAEL DAVID Assistant Member Memorial Sloan Kettering Cancer Center, United States B.Sc. SUNY Stony Brook Ph.D. The Weizmann Institute of Science Postdoc Princeton University My lab is interested in investigating how protein posttranslational modifications (PTMs) regulate cellular function and how perturbations to these PTM processes can lead to different pathologies. We focus on histone proteins, which package the eukaryotic genome and act as key regulators of all DNA-templated processes including transcription, replication, and damage repair. To do so, we develop transformative methodologies that allow us to perform research with chemical precision at a biochemical resolution and in a physiological context. Using these tools, we tackle questions at the heart of the field including epigenetic response to microenvironmental changes, regulation of chromatin architecture, and epigenetic inheritance. Unraveling the intricacies of these pathways will lead to new understandings of fundamental cellular events and open the door to novel therapeutic avenues with far reaching implications in the prevention, diagnosis, and treatment of diseases such as cancer.



JOSEPH COTRUVO, JR. Assistant Professor and Louis Martarano Career Development Professor, Pennsylvania State University, United States A.B. Princeton University Ph.D. Massachusetts Institute of Technology Postdoc University of California, Berkeley The Cotruvo lab employs a combination of biochemical, biophysical, and chemical biology methods to understand selective recognition of metal ions in biological systems, with applications to important questions in health and the environment. In one example (highlighted in this issue), we study how bacteria that depend on lanthanides for growth acquire, traffic, and utilize these metal ions in the presence of more abundant metal ions with a similar size or charge, such as Ca(II) and Fe(III). Our interests span from fundamental biological coordination chemistry to bioengineering applications for rare earth element mining and recycling. We are also working to develop new tools with which to selectively image Mn(II) and Fe(II) within cells, with applications in studying metal dynamics at the host−pathogen interface and in neurodegenerative disease.



SHEEL C. DODANI Assistant Professor, The University of Texas at Dallas, United States B.S. The University of Texas at Dallas Ph.D. University of California, Berkeley Postdoc California Institute of Technology The Dodani lab is building and applying a new chemical biology toolkit to identify the cellular stores, protein targets, and signaling roles of biologically relevant anions. Current projects are focused on the development of small molecule, macromolecular, and genetically encoded biosensors to capture a molecular level picture of anions, like chloride, at the cellular level. With these tools, we will not only define the design criteria required for aqueous anion detection but will also make fundamental contributions to understanding the roles of anions in human health and disease, paving the way for the development of anion targeted diagnostics and therapeutics.



SHEENA D’ARCY Assistant Professor, The University of Texas at Dallas, United States B.S. Advanced (Honors) University of Sydney Ph.D. University of Cambridge HHMI at Colorado State University



AMANDA E. HARGROVE Assistant Professor, Duke University, United States B.S., Trinity University 2

DOI: 10.1021/acs.biochem.8b01293 Biochemistry 2019, 58, 1−6

Biochemistry

Editorial

Ph.D., University of Texas at Austin NIH Postdoctoral Fellow, California Institute of Technology The Hargrove lab harnesses the unique properties of small organic molecules to study the structure, function, and therapeutic potential of long noncoding RNAs (lncRNAs). The discovery of these fascinating biomolecules has caused a paradigm shift in molecular biology and speculation as to their role as the master drivers of diseases like cancer. At the same time, very little is known about their structure and function, leading some to call the field a veritable Wild West. Small molecules are the perfect tools for such exploration, and the Hargrove lab is employing methods from organic synthesis, assay development, and molecular pattern recognition to RNA biochemistry and cell biology to elucidate fundamental principles behind selective RNA−small molecule recognition and apply them to these exciting targets.

shed light on a fundamental aspect of ribosome function and will provide a handle for designing next-generation antibiotics.



MAGNUS JOHANSSON



JAEHOON KIM



JUNG-AE KIM

Principal Investigator, Uppsala University, Sweden M.S., Ph.D. Uppsala University Postdoc Stanford University From decades of biochemical and structural approaches, a detailed picture has been painted of how ribosomes efficiently and accurately catalyze the assembly of amino acids into proteins. However, we have limited understanding of the dynamics of the protein synthesis machinery inside the cell and its interplay with other intracellular processes. In my lab, we make use of the vast knowledge acquired from in vitro biochemical experiments to develop new live-cell singlemolecule tracking techniques to study detailed reaction kinetics of the protein synthesis machinery. By following the diffusion of single molecules, we can observe transitions between different binding states and hence measure the kinetics of molecular processes directly, in real-time, in growing bacteria. Ongoing projects relate to cotranslational targeting of proteins to the membrane and the dynamic effects of antibiotic drugs on protein synthesis.



JIAN HU Assistant Professor, Michigan State University, United States B.S. Beijing Medical University Ph.D. Peking University Postdoc Florida State University & Yale School of Medicine The Hu lab strives to address critical issues in metal homeostasis closely related to human health by using a combination of structural, biochemical, biophysical, and cell biological approaches. The current study focuses on the Zrt/ Irt-like protein (ZIP) transition-metal transporters, which are central players in human zinc metabolism and broadly associated with diseases including cancers. Our goal is to clarify the metal transport mechanism, identify the molecular determinants of substrate specificity, and establish the molecular underpinnings of transporter regulation. The other ongoing projects include metalloenzymes (lactate racemase and ethylene-forming enzymes) and a metal receptor (calcium sensing receptor). We are also interested in targeting a lipid kinase family for drug discovery. We hope these efforts will lead to a better understanding of human diseases, novel therapies, and innovative approaches to environmental protection.

Assistant Professor, Korea Advanced Institute of Science and Technology, Korea B.S., M.S. Korea Advanced Institute of Science and Technology Ph.D. The Rockefeller University Postdoc The Rockefeller University My laboratory studies the functional and mechanistic aspects of epigenetic factors in eukaryotic transcription. We aim to determine the nature of histone modifications and mechanism of action of chromatin-modifying enzymes and histone modification-binding proteins that directly regulate target gene expressions in response to various developmental and stress stimuli by using biochemical and genetic analysis tools.



AXEL INNIS Group Leader, European Institute of Chemistry and Biology− Inserm, France B.Sc. (Honors) University of Bristol Ph.D. University of Cambridge Postdoc NCBS and Yale University−HHMI My group seeks to understand how different types of naturally occurring and synthetic peptides regulate bacterial protein synthesis, with a particular focus on the acquisition of antibiotic resistance and on interspecies communication within polymicrobial communities. Systems studied include antimicrobial peptides produced by the host immune response of insects, plants, and vertebrates, as well as arrest peptides, a class of nascent polypeptides that can sense and respond to different metabolites in the environment. To study these peptides, we use a combination of structural biology, biochemistry, directed evolution, and computational biology. A major focus is to assess the diversity and biological functions of arrest peptides across different bacterial species, with the aim of deciphering the arrest code underlying nascent chain-mediated translational arrest. Understanding this unique form of gene regulation will

Senior Scientist/Principle Investigator, Korea Research Institute of Bioscience and Biotechnology, Korea B.S. Korea University M.S. Korea University Ph.D. Brandeis University Postdoc Rockefeller University Research in our lab focuses on understanding how epigenetic mechanisms regulate the development of human diseases. By employing functional genomic screening methodologies with CRISPR/Cas9 and shRNA libraries, we attempt to identify (epi)genetic factors involved in epigenetic reprogramming to induce a cellular pathological state. The molecular mechanisms underlying the functional contributions of identified factors to given disease models are further investigated with diverse experimental tools. We are currently working on discovering epigenetic factors involved in cancer progression, which have potential as therapeutic targets. Our long-term goal is to provide a clue to the development of a new clinical strategy based on the epigenetic landscape in pathological conditions of human diseases. 3

DOI: 10.1021/acs.biochem.8b01293 Biochemistry 2019, 58, 1−6

Biochemistry



Editorial

HAJO KRIES Junior Research Group Leader, Leibniz Institute for Natural Product Research and Infection Biology (HKI Jena), Germany B.Sc. University of Geneva M.Sc., Ph.D. ETH Zurich Postdoc John Innes Centre My lab aims to develop novel methods for the biosynthetic design of natural products. We are particularly interested in the assembly line biosynthesis of nonribosomal peptides, which are a prolific source for peptide natural products with antibiotic and other biological activities. Nonribosomal peptide synthetases (NRPSs) generate a large structural diversity of natural products that we seek to expand even further by enzyme engineering. In the process from a design idea to a tailored synthetase, we use mechanistic enzymology and structural biology to locate bottlenecks and directed evolution to remove them. By unlocking tailored bioactivities with robust protocols for the combinatorial biosynthesis of nonribosomal peptides, we envision overcoming the alarming shortage of effective antibiotic drugs.

The Laurino lab strives to understand evolution of proteins at the molecular level. Understanding the evolutionary frameworks that create new functions in existing proteins is important since it lays the basis for design or engineering of proteins for new purposes. We have currently two scientific programs. The first is aimed at studying the evolution of cofactor binding pockets in different enzyme folds and how their specificities drive the evolution of entire pathways for a specific cofactor rather than others. Ultimately the goal for this program is to engineer one of these pathways. The second program interrogates the basis of coevolution for biological systems where one part coevolves together with many counterparts. We seek to understand how this coevolution drives new signaling mechanisms inside the cell.



CAROLE LINSTER Research Group Leader, University of Luxembourg, Luxembourg B.Sc., M.Sc., Ph.D. Université Catholique de Louvain Postdoc University of California, Los Angeles A major driving force behind the research in my group comes from the hundreds of predicted enzymes that remain without an identified function, even in well-characterized organisms such as Saccharomyces cerevisiae or humans. These “unknown” enzymes and the complexity of the intracellular metabolome suggest that important gaps persist in our understanding of (even primary) metabolism. We combine comparative genomics, systems genetics, metabolomics, and classical biochemical approaches to uncover and characterize new metabolic enzyme functions, especially in relation to metabolite damage and repair. Nondesired chemical reactions and enzymatic mistakes constantly generate noncanonical metabolites in our cells, and a growing list of enzymes preventing their accumulation is being uncovered. The vital importance of the latter process is demonstrated by severe inherited diseases resulting from metabolite repair deficiencies.



MARKITA LANDRY Assistant Professor, University of California, Berkeley, United States B.S. Chemistry, University of North Carolina, Chapel Hill B.A. Physics, University of North Carolina, Chapel Hill Certif icate in Business Administration, University of Illinois at Urbana−Champaign Ph.D. University of Illinois at Urbana−Champaign The Landry lab exploits the highly tunable chemical and physical properties of nanomaterials for the creation of biomimetic structures for molecular imaging and gene editing. Specifically, we synthesize nanoscale probes for imaging dopamine and serotonin to understand the kinetics of neuromodulation in the brain. We also synthesize nanomaterials for the delivery of genes and proteins in agriculturally relevant plants, to accomplish genome editing in crops.





MICHAEL LATHAM Assistant Professor, Texas Tech University, United States B.S. Hampden-Sydney College Ph.D. University of Colorado, Boulder Postdoc University of Toronto The Latham laboratory is interested in probing the structure, dynamics, and function relationships present in large macromolecular complexes. To do so, we combine solution state nuclear magnetic resonance (NMR) spectroscopy on protein side chain methyl groups, which can report on the structure and dynamics of systems approaching 1 megadalton in mass, with a variety of biochemical and biophysical methods. Our current focus is the Mre11-Rad50 complex, a macromolecular assembly that finds DNA double-strand breaks and assists in the process of DNA damage repair. Our goal is to understand the various structural and dynamic transitions that underlie the many activities of this complex.

PATRICK MÜ LLER Max Planck Research Group Leader, Friedrich Miescher Laboratory of the Max Planck Society, Germany M.Sc. Georg August University Göttingen Ph.D. Max Planck Institute for Biophysical Chemistry Postdoc Harvard University Emmy Noether Research Group Leader, Max Planck Institute for Developmental Biology The research of my laboratory is based on a systems biology approach that combines theory and quantitative experimentation to understand how signaling networks control gene expression patterns. We focus on the signaling systems that pattern the earliest axes during animal development, and we address three major questions in zebrafish and mouse embryonic stem cells: First, how is the transport of signaling molecules through tissues regulated? Second, how do signaling systems self-organize to generate patterned tissues from an initially homogeneous cell population? Third, how do signaling systems generate the correct tissue proportions in differently sized individuals? The nanobody-based tools presented in the accompanying paper open new avenues to modulate diffusiondependent transport processes and will help us to address the role of signal diffusion during vertebrate development.



PAOLA LAURINO Assistant Professor, Okinawa Institute of Science & Technology Graduate University, Japan B.S./M.S. Milan University Ph.D. ETH Zürich Postdoc Weizmann Institute of Science 4

DOI: 10.1021/acs.biochem.8b01293 Biochemistry 2019, 58, 1−6

Biochemistry



Editorial

THOMAS J. PUCADYIL Associate Professor, Indian Institute of Science Education and Research, Pune, India M.Sc. Maharaja Sayajirao University, India Ph.D. Centre for Cellular and Molecular Biology, India Postdoc The Scripps Research Institute The lipid bilayer is unique in its ability to resist rupture. This property lies at the heart of evolution choosing this material to contain life. However, all living cells display an active capacity to overcome the bilayer’s resilience to rupture. This is apparent from the fact that all cells manage vesicular transport, organelle formation, and cell division, processes that required active bending and rupture of the cell membrane possibly involving specialized protein machines. Our research is focused on identifying such protein machines and their mechanism of action. For this, we use a novel supported membrane template that displays an array of membrane nanotubes, which allows the analysis of membrane fission reactions in real time.

lysosome positioning with a particular focus on the role of small GTP-binding proteins of Rab and Arf-like (Arl) family and their effectors in this pathway. We have identified novel effectors of the lysosomal small G protein, Arl8, that mediate vesicle tethering to lysosomes and recruit microtubule motors to mediate lysosome motility. A second focus of the lab is to study the cellular function of Hook proteins that are adaptors of the microtubule motor dynein and regulate dynein function in organelle motility and cell division.



ARUN K. SHUKLA Associate Professor and Joy Gill Chair Professor, Indian Institute of Technology, India M.Sc. Jawaharlal Nehru University Ph.D. Max Planck Institute of Biophysics Postdoc, Duke University Medical Center The research program in my laboratory is focused on understanding the structural basis of activation and signaling of G Protein-Coupled Receptors (GPCRs). These receptors are the main conduit of information transfer across the cell membrane, and they are intricately involved in almost every physiological and pathophysiological process in the human body, such as cardiovascular regulation, immune response, neurotransmission, behavior and mood regulation. About half of the currently prescribed drugs target this class of receptors, including alpha and beta blockers, angiotensin receptor blockers and anti-histamines. GPCR-targeting drugs are used in congestive heart failure, hypertension, asthma, allergies, schizophrenia, Parkinson's disease and cancer. We utilize synthetic chaperones generated through combinatorial biology and directed evolution approaches to capture and visualize distinct conformational states of GPCRs and their signaling complexes. Our research projects involve a multifunctional approach including cellular signaling, protein biochemistry, receptor pharmacology and structural biology.



ANDREA RENTMEISTER Associate Professor, University of Münster, Germany B. Eng. Technical University of Graz M.Sc./Ph.D. University of Bonn Postdoc California Institute of Technology Research in my group focuses on RNA biochemistry at the interface of chemistry and biology. We aim to understand and ultimately control processes affecting mRNA expression and turnover at the molecular level. To this end, we develop chemical and biochemical tools for manipulation, analysis, and control of mRNA in living cells and in vivo.



GUILLAUME ROMET-LEMONNE CNRS research director, Institut Jacques Monod, France Engineer, Ecole Centrale Paris Ph.D. Université Paris-Sud Postdoc FOM-Amolf Together with Antoine Jegou, I lead the two-headed group “regulation of actin assembly dynamics,” working at the interface between biophysics and biochemistry. Our research focuses on the biochemical and mechanical regulation of the actin cytoskeleton, through in vitro experiments with purified proteins. In particular, we have initiated and developed over the past years a technique combining microfluidics and optical microscopy, which we use to monitor and manipulate individual actin filaments. This powerful approach provides new insights into a number of molecular mechanisms, by looking at individual reactions in physiologically relevant contexts.



PRATYUSH TIWARY Assistant Professor, University of Maryland, College Park, United States B.S. Indian Institute of Technology (Banaras Hindu University) M.S./Ph.D. California Institute of Technology Postdoc ETH Zürich and Columbia University My lab consists of a group of chemists, biophysicists, and physicists. Together our aim is to develop and apply the next generation of all-atom resolution simulation methods, based on statistical mechanics and artificial intelligence, that can transcend time scales from femtoseconds to days. Many biomolecular systems involve processes with intertwined spatiotemporal resolutions, making it hard to probe them using traditional experimental tools. It has been a holey grail to study these using all-atom simulations, but these can go up to only a few microseconds even with most powerful supercomputers. Our methods break this barrier and give a vantage point from which to directly observe mechanisms of different fundamental problems including but not limited to ligand− protein and DNA−protein dissociation, providing a detailed insight into their thermodynamics, kinetics, and pathways.



MAHAK SHARMA Associate Professor and Wellcome Trust-DBT India Alliance Intermediate Fellow, Indian Institute of Science Education and Research (IISER) Mohali, India B. Tech. Guru Gobind Singh Indraprastha University Ph.D. University of Nebraska Medical Center, Omaha Postdoc Brigham & Women’s Hospital/Harvard Medical School With the advent of compartmentalization, eukaryotic cells evolved “vesicular transport pathways” to open channels of communication between the different intracellular organelles. The primary focus of my research has been to elucidate mechanisms regulating vesicular transport to lysosomes and



ARTURO VEGAS Assistant Professor, Boston University, United States B.A. Cornell University Ph.D. Harvard University 5

DOI: 10.1021/acs.biochem.8b01293 Biochemistry 2019, 58, 1−6

Biochemistry

Editorial

Postdoc Massachusetts Institute of Technology/Children’s Hospital Boston The Vegas group pursues general and systematic approaches to developing targeted therapeutic carriers for the treatment of multiple human diseases. Small-molecule drugs excel at altering disease states at the cellular level, but their therapeutic benefits are often hindered by physiological barriers that impact their toxicity, efficacy, and distribution. The ability to overcome these barriers can make major differences in both the safety and effectiveness of a therapeutic. Projects in the lab are focused on developing novel chemical tools, materials, and approaches for targeting therapeutics to diseased tissues, with an emphasis on cancer and diabetes. These new tools will facilitate studies in the lab to understand mechanisms that control the physiological distribution of therapeutics and inform future targeting element design.

study of highly dynamic processes like autophagosome formation and are beneficial for investigating subcellular or subtissue physiology. His lab has developed a set of sitespecific protein modification methods, facilitating investigation of weak protein−protein interactions, host−pathogen interactions, spatiotemporal imaging of GTPase activity, etc. Using a combination of chemical and biological approaches, his lab has elucidated new mechanisms of autophagosome formation and Rab membrane targeting.



ERIK YUKL Assistant Professor, New Mexico State University, United States B.S. Pacific University Ph.D. Oregon Health and Science University Postdoc University of Minnesota The widespread emergence of antibiotic resistance among pathogenic bacteria has prompted a search for novel bacterial targets for antibiotic development. The Yukl lab is interested in pursuing mechanisms of zinc import through ATP binding cassette (ABC) transporters as such a target. We use a variety of structural and spectroscopic techniques in addition to in vivo functional assays to determine mechanisms of zinc binding and transport at the molecular level. Of particular interest are organisms that employ multiple ATP transporters for zinc as well as periplasmic metallochaperones, the precise functions of which remain somewhat enigmatic.



OPHELIA S. VENTURELLI Assistant Professor, University of Wisconsin Madison, United States B.S. Stanford University Ph.D. California Institute of Technology Postdoc University of California, Berkeley The Venturelli multiscale systems and synthetic biology lab integrates experiment and computational modeling to investigate the evolutionary design principles of biomolecular networks and microbial communities. We aim to exploit engineering and biological design principles to control microbial community dynamics and functions. Our research combines multiplexed measurements of single cells and populations with concepts from nonlinear dynamical systems, control theory, and multiobjective optimization. The lab is also developing novel methods to study the spatiotemporal behaviors of microbial communities.



QI ZHANG Professor, Fudan University, China B.S. Fudan University Ph.D. Shanghai Institute of Organic Chemistry Postdoc University of Illinois at Urbana−Champaign Dr. Zhang’s research program focuses on the biosynthesis and modes of action of several classes of antimicrobial compounds, such as aminoglycosides, lipopeptides, and ribosomally synthesized and post-translationally modified peptides (RiPPs). We aim to reveal in detail their biosynthetic chemistries to discover novel bioactive compounds by genome mining and by bioengineering efforts and to decipher their modes of action and resistance mechanisms. Another research interest in the Zhang lab is the radical S-adenosylmethionine superfamily enzymes. We strive to understand their biological functions and mechanisms and to manipulate these enzymes to achieve novel catalytic activities.



ZOË WALLER Senior Lecturer, University of East Anglia, United Kingdom M.Chem. University of Bradford Ph.D. University of Cambridge I am absolutely fascinated by alternative DNA structures and their applications both in biology and also nanotechnology. DNA−ligand interactions particularly interest me because of how small molecules have been used traditionally as pharmaceutical interventions for treatments and cures for diseases. This work shows how commonly used ligands to target a G-quadruplex can also interact with another DNA structure, called the i-motif.



Alanna Schepartz*

YAOWEN WU Professor, Umeå University, Sweden B.Sc. Sun Yat-sen University M.Sc. Tsinghua University Ph.D. Max Planck Institute of Molecular Physiology Postdoc King’s College London The Wu lab focuses on developing novel chemical approaches, including protein chemical modification and chemical and chemo-optogenetics, and using these tools to tackle biological problems with a focus on membrane trafficking and autophagy. His lab has pioneered the development of chemo-optogenetic tools to enable manipulation of protein or organelle function in the cell with a high spatiotemporal precision. These tools have facilitated the



Department of Chemistry, Yale University, 225 Prospect Street, New Haven, Connecticut 06520, United States

AUTHOR INFORMATION

Notes

Views expressed in this editorial are those of the author and not necessarily the views of the ACS.

6

DOI: 10.1021/acs.biochem.8b01293 Biochemistry 2019, 58, 1−6