Q&A Voices of chemical biology Agreeing on a precise definition of chemical biology has been a persistent challenge for the field. We asked a diverse group of scientists to “define chemical biology” and present a selection of responses. Chemical biology is an area of research in unique ability of chemists to not only study Chemical biology, in the broadest sense, which chemical and biological concepts but also create new forms of matter at the addresses the interface between chemistry and tools interact synergistically in the molecular level for societal beneft. and biology and sometimes physics. pursuit of new discoveries or technologies. Christopher J Chang It provides a way to explore biological Carolyn R Bertozzi University of California, Berkeley and phenomena based on physicochemical Stanford University, Palo Alto, California, USA HHMI, Berkeley, California, USA principles. Amitabha Chattopadhyay Chemical biology is the exploration of Chemical biology is destined to answer Centre for Cellular and Molecular Biology, mechanisms governing living systems questions in biology in the broadest sense Hyderabad, India using tools, methods and analytical by using chemistry, chemical techniques or frameworks involving molecular novel chemical probes, but with the biology Chemical biology is the application of structures. Tis includes the classic in the center of the work. Chemical biology chemistry to investigate biological systems defnition of chemical biology, which is difers from biochemistry because the or to solve biological problems. Whereas the use of synthetic organic chemistry to latter is usually defned as a disassembled traditional disciplines, such as organic create small-molecule probes of biological and reconstituted system of biomolecules chemistry and biochemistry, have a vertical processes; it also encompasses a broader whereas chemical biology might be focus, applying techniques to discipline- set of eforts in the growing chemical targeting or attempting to understand specifc questions, chemical biology has a biology community, such as molecular chemistry in intact cells, tissues or whole more horizontal focus, borrowing tools from pharmacology, single-molecule biophysics, animal systems. organic chemistry, biochemistry, analytical synthetic biology, chemical proteomics Carsten Schultz chemistry, molecular biology, structural and chemical systems biology. In short, European Molecular Biology Laboratory, biology and/or cell biology to study I think of chemical biology as the use of Heidelberg, Germany biological questions at the molecular level. chemical methods to understand biological Rebecca A Butcher processes. Chemical biology is using biology to do University of Florida, Gainesville, Florida, USA Nature America, Inc. All rights reserved. America, Inc. Nature Brent R Stockwell new chemistry and using chemistry to 5 Columbia University, New York, New York, USA probe biology. Chemical biology is the discipline focused Pamela A Silver on understanding the fundamental © 201 It is chemistry brought to life: the science Harvard Medical School, Boston, mechanisms of various biological processes of applying chemistry to understand and Massachusetts, USA at the molecular level. Tis knowledge perturb biological processes. can be used to control and modulate these npg Stefan Kubicek Chemical biology is focused on the biological processes, especially disease- CeMM Research Center for Molecular development of new molecules or approaches relevant biological pathways. Medicine of the Austrian Academy of Sciences, that are purposefully and intentionally Seung Bum Park Vienna, Austria designed to address specifc gaps in biological Seoul National University, Seoul, Korea knowledge. In other words, ‘tool making’ Chemical biology is both the application occurs hand in hand with ‘tool using’. To paraphrase Sydney Brenner, chemical of chemical approaches and tools to Jason E Gestwicki biology is that feld of science that is biology and the application of biological University of California, San Francisco, conducted by chemical biologists. molecules and systems to chemistry. San Francisco, California, USA Brian K Shoichet Chemical biologists ofen invent new University of California, San Francisco, tools and methods, but they also pursue Chemical biology is a science in pursuit San Francisco, California, USA pure biological research in a way that is of biological and medical questions colored by the perspective of a chemist. A that are less amenable to being tackled Chemical biology is a broad area of key strength of chemical biology is that it with (or refractory to) classical methods research representing the interface between is not hampered by rigid defnitions, and such as those routinely used in cell chemistry and biology. Chemical tools and can therefore embrace new ideas and shif biology, genetics and biochemistry. Te concepts are used to understand and/or directions more freely than other felds. unique properties of the chemical tools control biological processes at the molecular Bryan C Dickinson suggest that chemical biology not only is level. Tese tools can be synthetic, such as University of Chicago, Chicago, Illinois, USA complementary to other sciences but also the generation of small or large synthetic has a cutting-edge advantage in certain probes and natural biomolecules, or Chemical biology involves viewing the investigations of biology. they can be analytical, including diverse world around us, the living organisms Gabriela Chiosis spectroscopic methods and informatics and their environment, through the lens Memorial Sloan Kettering Cancer Center, and computational approaches. Chemical of a chemist, and taking advantage of the New York, New York, USA biology can be used to investigate and 378 NATURE CHEMICAL BIOLOGY | VOL 11 | JUNE 2015 | www.nature.com/naturechemicalbiology Q&A manipulate reactions and molecular to probe, uncover and understand For me, chemical biology is the science interactions in vitro, but increasingly its biological processes could be considered of how chemical substances infuence or tools are used to target biological processes chemical biology. Te key is learning new control biology. Te ‘biology’ infuenced inside living cells and organisms. biology. by chemistry can be either an isolated Sabine L Flitsch Chuan He biological molecule, for instance a nucleic The University of Manchester, Manchester, UK University of Chicago, Chicago, Illinois, USA acid, or a larger entity, such as a whole cell or an organism. Te ‘chemical substances’ Chemical biology is a discipline in which Chemical biology addresses the could be small or large molecules and chemical tools, methodologies and interface between physical chemistry may include both organic and inorganic principles are applied to biological systems. and biochemistry. It uses the atomistic components. Jin Zhang understanding of chemistry on molecules Lene B Oddershede Johns Hopkins University, Baltimore, and in molecular interactions and applies it Niels Bohr Institute, Copenhagen, Denmark Maryland, USA to defned and reduced biological systems. Tis knowledge is then used to describe In my mind, chemical biology is the As is the case with many rapidly developing biological systems on a higher scale. application of small-molecule probes, which felds, the defnition of chemical biology has Anna Moroni are complementary to the tools available evolved. Although it was originally associated University of Milan, Milan, Italy from biologists, to interrogate biomolecular with the use of small molecules to probe Gerhard Thiel targets and their associated cellular pathways biological pathways, it has been inspiring Technical University of Darmstadt, with a view to obtaining new biological to see chemical biology expand to embrace Darmstadt, Germany insights. Its origins are in chemistry, but are concepts such as the use of biological ported over toward answering biological principles to advance chemistry, the precise Chemical biology is solving biological questions. Te goal of chemical biology is manipulation of macromolecules to study problems with chemical tools, or one of interrogation and ‘illumination’, and biology and inform novel therapeutics, and developing the tools for elucidating not necessarily a therapeutic outcome. many others. For me, chemical biology is or formulating unexploited biological Arthur Christopoulos not simply a research feld, but a philosophy questions. Monash University, Parkville, Australia about discovering, synthesizing and Young-Tae Chang manipulating molecules to illuminate life and National University of Singapore, Singapore Chemical biology is the application of improve the human condition. chemical and physical principles and David R Liu experimental and theoretical approaches Harvard University, Cambridge, for dissecting the molecular detail of the Massachusetts, USA How would you define biological reactions and interactions in living systems. In my opinion, chemical biology is chemical biology? Barbara Imperiali Nature America, Inc. All rights reserved. America, Inc. Nature characterized by its methodologies. Massachusetts Institute of Technology, 5 For example, in addition to molecular Cambridge, Massachusetts, USA biological techniques, organic chemical Chemical biology is the development and © 201 techniques are ofen used for analyses of application of novel chemistry to the study Chemical biology is a ‘multiphase’ discipline the functions of biomolecules in cells and of biological phenomena and processes. By lodged