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Does History Repeat Itself? The Emergence of a New Discipline Laura M. C. Barter, David R. Klug, and Ru¨diger Woscholski* Chemical Biology Centre, Imperial College London, Exhibition Road, London SW72AZ, United Kingdom
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he influence of chemistry in the development of the life sciences led to the emergence of biochemistry departments in many institutions and organizations. This subject focused on the “study of the chemistry of life processes” (1) and over time became independent of its original disciplines and established subspecializations in its own right. Biochemistry continues to be an area of expansion, with many degree courses offered to students around the world. Biochemistry was initially a truly interdisciplinary area, but it evolved quickly and in due process distanced itself increasingly from its roots within chemistry to become a “biological” entity. Chemical biology is another, more recent, offshoot from chemistry that aims to combine the physical and the life sciences (2). By our definition, however, many important distinctions exist between the emerging discipline of chemical biology and the nowestablished disciplines within biochemistry. In particular, we at the Chemical Biology Centre (CBC) in London characterize our approach as multidisciplinary rather than interdisciplinary. Such progress requires a mastery of the cutting-edge physical and biological sciences; the best and most relevant parts of each must be combined to solve well-identified problems. If history repeats itself, this new approach of applying chemistry to solve biological problems will become a substantial and evolving research area; but will it, and should it, lead to the establishment of new departments? We argue that the creation of new departments www.acschemicalbiology.org
and undergraduate courses is not necessarily the way forward. We believe that the modern discipline of chemical biology will grow via new and flexible research structures that capture the quantitative mature approach prevalent in physics, chemistry, and engineering and apply it to the rapidly evolving fields of biology, biochemistry, and medicine. The demand is increasing for a cohort of scientists for whom multidisciplinary thinking is the norm in both academic and industrial research. Imperial College London, the Institute of Cancer Research, and the Cancer Research UK London Research Institute, all highly ranked research institutions in Europe, joined forces to create the CBC five years ago. This was driven by the desire to bring together those scientists whose research activities would be particularly synergistic. The key objectives of the CBC were both to develop multidisciplinary research programs across the life science-physical science interface and to provide training for that cohort of researchers seen as so vital to postgenomic science and technology. The CBC offers lecture courses, examinations, seminars, workshops, and research training for physical scientists who wish to work in the chemical biology area with a particular emphasis on new approaches in molecular medicine. The CBC also supports the devel-
*Corresponding author,
[email protected].
Published online December 15, 2006 10.1021/cb600468u CCC: $33.50 © 2006 by American Chemical Society
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Box 1. CBC Training Courses M.Res./Ph.D. in Protein Membrane Chemical Biology. This course starts with a fulltime, one-year M.Res. qualification in membrane and protein chemical biology. Training includes a multidisciplinary research project, taught courses in advanced biochemistry and biomolecular techniques, specialist lectures in transferable skills, and group discussion sessions. CBC DTC continues to oversee a three-year Ph.D. assignment, which leads to a degree awarded by Imperial College London. Ph.D. Studentships in Single-Cell Proteomics. Six Ph.D. studentships affiliated with the DTC are assigned to support this EPSRC-funded CBC project, which aims to create an unrivaled suite of technologies for the study of single cells using proteomic approaches. M.Res. in Bioimaging Sciences. This full-time, one-year M.Res. course features a nine-month multidisciplinary research project and taught lecture courses. The fundamentals of modern imaging methodologies are covered, including techniques and applications in medicine and the pharmaceutical industry, and the chemistry behind imaging agents and biomarkers. M.Res. in Biomedical Physical Chemistry. This full-time, one-year course enables students to bridge the gaps of language, perspective, and methodology between the life and physical sciences. A nine-month multidisciplinary research project, taught courses in physical and chemical technologies, and training in biomedical research, advanced biochemistry, and practical biomolecular techniques are included.
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degrees in the physical sciences (chemistry, physics, engineering, etc.) to equip them with the necessary knowledge, skills, and language to confidently apply their physical science backgrounds to problems in the life sciences. In this respect, we looked more to the waves of physical scientists who emerged to establish fields such as modern structural biology than to the growth of biochemistry departments. The CBC is particularly aware that many students educated in the physical sciences are keen to be trained in projects that are focused on problems in the life sciences. The CBC’s main strategy is to attract this pool of physical scientists, train them to use their skills and knowledge to solve biological problems with advanced physical sciences approaches, and modify and develop those approaches accordingly. To achieve these objectives, the CBC Doctoral Training Centre (DTC) was established with funding from the Life Sciences Interface Programme of the EPSRC. The focus of the DTC is on chemical biology at, within, or BARTER ET AL.
Image courtesy of the CBC
opment of new tools and techniques and facilitates their translation among traditional academic institutions and between academia and industry. Both tool development for the life sciences and the quantitative investigation of biological engineering rules rely on a close interaction and collaboration between physical scientists and life scientists. As a virtual center, the CBC looks for new ways for these researchers to interact. It has a policy of zero barrier to entry, zero barrier to exit with more than 50 research groups currently involved in CBC research projects. The CBC is also home to various targeted research programs such as the Non-Specific Drug Binding Initiative funded by GlaxoSmithKline and the Single Cell Proteomics Project supported by the Engineering and Physical Sciences Research Council (EPSRC) and the Biotechnology and Biological Sciences Research Council. In the context of graduate education, a major priority for the CBC was to create graduate programs for students who have
near cell membranes. This Ph.D. program is complemented by three master courses, which either precede the Ph.D. education, or, in some cases, function as a stand-alone training for those students wishing to broaden their knowledge and understanding in the art of multidisciplinary research without the commitment of undertaking a Ph.D. (See Box 1 for further information on the Ph.D. and master’s in research (M.Res.) courses offered by the CBC DTC.) The courses under the CBC umbrella provide physical science graduate students with (i) cross-departmental, crossinstitutional, multidisciplinary training toward careers at the physical science/life science interface, (ii) the necessary guidance and experience to apply their physical science skills to problems in the life sciences, and (iii) the ability to move with confidence into biological, biotechnological, and biomedical research, bringing them relevant disciplines, skills, and approaches of their undergraduate training. For the CBC to achieve its aims, input from a broad range of disciplines is essential. It is clear that advances will depend on the collaborative efforts of biochemists, chemists, medics, physicists, and engineers. Thus the M.Res. programs are designed to bridge the “cultural” divide that can exist between these disciplines because of differences in language, perspective, and methodology. The courses foster development within the type of multi-
CBC chemistry laboratory www.acschemicalbiology.org
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FOCUS Box 2. Format of CBC M.Res. Courses Taught Component. A fixed lecture program of core courses in the first term is followed by optional courses to complement the research project undertaken by the student in the second term. Research Project. In October, the nine-month multidisciplinary research project is chosen. Students present a literature report on the topic of their research project by the end of the first term, a talk in July or August, and a final thesis in September. M.Res. Conference. A meeting for all M.Res. students to present their research projects and to learn about the work carried out by their fellow cohorts. Keynote speakers from other institutions are also invited. Research Seminars and Colloquia. The chemistry department organizes monthly research seminars by leaders in particular fields. Students interact and discuss scientific issues with these visitors to the department, as well as with staff members. The CBC organizes two or three afternoon colloquia annually, which focus on a particular research area. Visiting Professors—Advanced Courses. The CBC invites two visiting professors every year for a two-month appointment. The professors deliver eight hours of lectures on their areas of research. Interactions between the students and the professors are encouraged. disciplinary setting that students will expect to enter on completion of the degree. The courses have also been designed to meet the demands for both breadth of knowledge and the physical techniques employed in this area of work. Moreover, they provide a depth of experience in experimental practice that is gained from undertaking a single nine-month research project. Students concentrate on one research project, which is jointly supervised by at least one physical and one biological scientist. The projects are expected to involve the research laboratories and teams of both collaborating supervisors. This allows the students to benefit from interaction with supervisors as well as postdoctoral and postgraduate researchers from both disciplines. This multidisciplinary approach provides a hands-on experience of biological techniques and systems that is both challenging and rewarding for physical science graduates. The format of a single project running through the entire year of the M.Res. course has been adopted primarily because it takes time to become accustomed to working in a multidisciplinary environment. A single nine-month project is www.acschemicalbiology.org
challenging but offers the satisfaction of a real scientific achievement at the end. A depth of knowledge and confidence is gained that cannot readily be found in structured practical work or shorter projects. This direct experience of multidisciplinarity in research is something that we regard as key to the development of modern chemical biology.
The training that the M.Res. students receive is complemented by a structured lecture program and seminars. Training is not limited to the M.Res. cohort of students. The CBC encourages all DTC students to meet, interact, and discuss scientific issues with visitors to the chemistry department and staff members by organizing colloquia, workshops, and student conferences. The CBC also runs a visiting professor program where a professor is invited to reside in the department for a period of up to two months, and interaction between the students and professor is encouraged. Students benefit from the stimulation of hearing about the most recent scientific advances from esteemed scientists, and lectures delivered by the professor widen the students’ scientific horizons. Moreover, contact with scientists from other institutions exposes students to a broader range of scientific approaches and attitudes. (See Box 2 on the format of the training and courses.) Specialist transferable-skills lectures also form part of the training. Students are trained in a wide range of transferable skills following exposure to the various teaching and learning aspects of the M.Res. courses, such as safety awareness, effective commu-
Box 3. CBC Transferable-Skills Courses The Joint DTCs’ Teamwork Course. An intensive course in teamwork, personal development, information gathering, and presentation, with a focus on networking and relationship building among Ph.D. students within the CBC DTC as well as with other DTCs. Elements include a business game about a biotechnology start-up company and a presentation exercise based on a research grant pitch. Science Communication Course. An intensive two-and-a-half day course directed by Gareth Mitchell, a lecturer in radio broadcast communication in the Science Communication Group at Imperial College London and a practicing scientific broadcaster for the BBC. Students develop skills on both sides of the camera and the microphone, as well as effective scientific writing under real-time pressure. Decision-Making Course. This course on the methodology and analysis of decision making follows models in the teamwork course. Specific business content, such as financial analysis, prepares students for working in pharmaceutical companies and other industries.
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Box 4. Contacts Chemical Biology Centre www.chemicalbiology.ac.uk, ⫹44 (0)20 7594 5880,
[email protected] M.Res. in Biomedical Physical Chemistry Laura Barter, ⫹44 (0)20 7594 1885,
[email protected] M.Res./Ph.D. in Protein Membrane Chemical Biology Rudiger Woscholski, ⫹44 (0)20 7594 5305,
[email protected] M.Res. Bioimaging Sciences Nick Long and Ramon Vilar, ⫹44 (0)20 7594 5781/7594 1967,
[email protected] or
[email protected] Department of Chemistry Doris Pappoe, ⫹44 (0)20 7594 5864,
[email protected]; online application: www.imperial.ac.uk/P1397.html nication, time and project management, and management skills. The Graduate School of Engineering and Physical Sciences at Imperial College London also provides transferable skills training. Examples of course topics include intellectual property management, personal organization and effectiveness, research ethics, and technical presentation skills. The CBC has also devised a suite of three transferable-skills courses, specifically for the DTC students, on science communication, team work, and decision making. These courses form the core of the students’ transferable-skills training. (See Box 3 for further information about these courses.) A number of multidisciplinary DTCs are currently running in the U.K. (Examples of DTCs funded by the EPSRC can be found at www.epsrc.ac.uk/PostgraduateTraining/ LSIDoctoralTrainingCentres/default.htm.) The CBC has already developed links with some of them, and we hope these interactions will continue to expand. For example, the CBC transferable-skills courses are given jointly with the DTCs in Warwick, Leeds/ Sheffield, Edinburgh, Glasgow, and Dundee. The courses not only bring together our cohort of DTC students but also facilitate networking and interdisciplinary communication with the other multidisciplinary life/ physical science DTCs. 740
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Our students have responded positively to this training program and are keen to embrace the opportunities provided by the CBC courses. An important indicator of success for the current courses in the CBC is the scientific output. We are delighted that research undertaken during this short ninemonth period of the M.Res. research project has resulted in several publications (3–9), one of which is in this issue (9). Almost all of our students in the DTC have yet to finish their Ph.D. work, so we expect that this publication list will grow over time. This will corroborate the multidisciplinary nature of the training offered by the CBC and the DTC. Chemical biology education is still in its infancy, and time will tell whether it will evolve into its own discipline. Postgraduate training will certainly be the quickest route to alleviating the lack of suitably trained physical scientists and deliver future leaders of chemical biology research. Although undergraduate training of the future will no doubt include more chemical biology, either through the introduction of corresponding modules within existing degree courses or through the creation of dedicated degree courses, it is unlikely to be the sole provider for the next generation of chemical biologists. We ourselves are focused on chemical biology as a postgraduate discipline for those with first-class expertise in disciplines such as chemistry and physics but who BARTER ET AL.
want to use this knowledge in a meaningful and useful way in a biological context. (See Box 4 for contact information.) The multidisciplinary environment of the CBC is designed to take these core strengths and train research cohorts who are each multidisciplinary in their own right. In this sense, every Ph.D. student is expected to be an expert in both an area of life science and an area of physical science. Chemical biology is therefore not for the faint of heart. REFERENCES 1. Berg, J. M., Tymoczko, J. L., and Stryer, L. (2006) Biochemistry, 6th ed., W. H. Freeman and Co., New York. 2. Larijani, B., Rosser, C. A., and Woscholski, R. (2006) Introduction, in Chemical Biology: Techniques and Applications (Larijani, B., Rosser, C. A., and Woscholski, R., Eds.) pp 1–10, John Wiley & Sons, Ltd., Chichester, U.K. 3. Treanor, B., Lanigan, P. M. P., Kumar, S., Dunsby, C., Munro, I., Auksorius, E., Culley, F. J., Purbhoo, M. A., Phillips, D., Neil, M. A. A., Burshtyn, D. N., French, P. M. W., and Davis, D. M. (2006) Microclusters of inhibitory killer immunoglobulin like receptor signaling at natural killer cell immunological synapses, J. Cell Biol. 174, 153–161. 4. Seddon, J. M., Squires, A. M., Conn, C. E., Ces, O., Heron, A. J., Mulet, X., Shearman, G. C., and Templer, R. H. (2006) Pressure-jump X-ray studies of liquid crystal transitions in lipids, Philos. Trans. R. Soc. London, Ser. A 364, 2635–2655. 5. Conn, C. E., Ces, O., Mulet, X., Finet, S., Winter, R., Seddon, J. M., and Templer, R. H. (2006) Dynamics of structural transformations between lamellar and inverse bicontinuous cubic lyotropic phases, Phys. Rev. Lett. 96, 108012-1–108012-4. 6. Ces, O., and Mulet, X. (2006) Physical coupling between lipids and proteins: a paradigm for cellular control, Signal Transduction 6, 112–132. 7. Baciu, M., Sebai, S. C., Ces, O., Mulet, X., Clarke, J. A., Shearman, G. C., Law, R. V., Templer, R. H., Plisson, C., Parker, C. A., and Gee, A. (2006) Degradative transport of cationic amphiphilic drugs across phospholipid bilayers, Philos. Trans. R. Soc. London, Ser. A 364, 2597–2614. 8. Burke, M. G., Woscholski, R., and Yaliraki, S. N. (2003) Differential hydrophobicity drives self-assembly in Huntington’s disease, Proc. Natl. Acad. Sci. U.S.A. 100, 13928–13933. 9. Rosivatz, E., Matthews, J. G., McDonald, N. Q., Mulet, X., Ho, K. K., Lossi, N., Schmid, A. C., Mirabelli, M., Pomeranz, K. M., Erneux, C., Lam, E. W.-F., Vilar, R., and Woscholski, R. (2006) A small-molecule inhibitor for phosphatase and tensin homologue deleted on chromosome 10 (PTEN), ACS Chem. Biol. 1, 780–790.
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