Program Review Challenges and Opportunities for Training the Next Generation of Biophysicists: Perspectives of the Directors of the Molecular Biophysics Training Program at Northwestern University

Abstract

Molecular biophysics is a broad, diverse, and dynamic field that has presented a variety of unique challenges and opportunities for training future generations of investigators. Having been or currently being intimately associated with the Molecular Biophysics Training Program at Northwestern, we present our perspectives on various issues that we have encountered over the years. We propose no cookie-cutter solutions, as there is no consensus on what constitutes the “ideal” program. However, there is uniformity in opinion on some key issues that might be useful to those interested in establishing a biophysics training program.

HISTORICAL OVERVIEW

The origins of the Molecular Biophysics Training Program at Northwestern can be traced back to the mid-1980s when the university made a successful coordinated effort to hire new faculty and develop state-of-the-art facilities for research in this field, which was emerging as one of the most exciting areas for groundbreaking discoveries. Molecular biophysics represented a new paradigm in that it required investigators to transcend traditional disciplinary lines and combine the perspectives of chemists, physicists, and biologists. It also called for the development of new graduate programs and curricula for training the next generation of researchers. A core group of faculty from the Department of Biochemistry, Molecular Biology and Cell Biology and the Department of Chemistry at Northwestern recognized these challenges and established in 1990 a formal molecular biophysics track within the respective graduate programs with partial funding from the NIH.

Befitting its multidisciplinary nature, the biophysics training program at Northwestern has expanded considerably from its modest beginnings. With the addition of more facilities and faculty from four other life science and engineering graduate programs, it now spans multiple departments and schools. These expansions created new challenges that included ensuring a uniform didactic experience for the trainees and crafting an identity for the trainees that is distinct from their parent graduate programs. These issues are discussed in detail below.

BACKGROUND AND PREPARATION

Given the lack of opportunities to major in biophysics at the undergraduate level at most institutions, a key question for trainee selection panels charged with identifying and recruiting talent is what constitutes the ideal preparation for indepth graduate studies. One school of thought holds that physical chemistry comes closest to serving this purpose. Somewhat surprisingly, this sentiment is not shared unanimously by us. As mentioned earlier, our biophysics program draws students from six major graduate programs in the life and chemical sciences and engineering. Significant barriers that preclude multidisciplinary training are uncommon at Northwestern and there have been examples of students with no physical chemistry or equivalent preparation who have gone on to do well in our program by taking appropriate remedial coursework. However, there is broad consensus that either some quantitative background at the undergraduate level or a demonstrated aptitude for quantitative issues is an important requisite for success in our program. Our trainees with undergraduate majors in chemistry, physics, engineering, and biology have done well in their graduate, postdoctoral, and independent careers. However, students with quantitative backgrounds in physical sciences typically respond better to the challenges of biophysics training than do those from traditional biological backgrounds. In the long term, interdisciplinary fields such as biophysics would be better served if there were a paradigm shift in undergraduate education in science and engineering with courses endeavoring to highlight key applications of fundamental concepts beyond their respective fields. These ideas could be incorporated within the framework of existing courses, or new courses could be developed exclusively for this purpose.

CORE CURRICULUM

Devising courses that constitute the core curriculum depends to a large extent on the type of training program and the cohort of students it seeks to serve. Standalone biophysics programs have the option of recruiting students with significant background and preparation in the physical and quantitative sciences. This provides an opportunity to focus the core curriculum on a mix of advanced physics and mathematics courses along with appropriate molecular and cell biology courses with the goal of encouraging the students to ask pertinent questions in a new discipline. Umbrella programs, which most biophysics training programs in the country including our program identify with, cater to a different cohort, one whose background and preparation is anchored more closely to biology and who are more likely to focus their research on the applications of biophysical methods to biological problems. These students typically need to enhance their quantitative skills and background, requirements that are fundamentally different from those described for the other group (above). Devising a common core curriculum for these rather divergent groups represents a major challenge.

The core curriculum for trainees in molecular biophysics at Northwestern has undergone significant evolution since the program was established. In its current form, the curriculum has withstood a limited test of time (slightly over 3 years) and has gained acceptance by students and faculty alike. It consists of an introductory course in biophysics and two advanced in-depth courses that cover methods in structural biology and biophysics. The introductory course covers macromolecular structure, various forms of spectroscopy, crystallography, electron microscopy, hydrodynamics and transport processes, single-molecule biophysics, and macromolecular machines. The advanced courses explore the theoretical underpinnings and practical applications of a variety of contemporary methods. Macromolecular NMR and crystallographic methods form the basis for one of the advanced courses while topics related to macromolecular structure, dynamics and interactions are covered in the other course, which is offered in a team-taught format with experts in 10 different areas leading the lectures and discussion. Topics in the latter course include binding thermodynamics (via fluorescence, calorimetry, and NMR) and kinetics (via surface plasmon resonance), extended X-ray absorption fine structure, Mössbauer and atomic absorption spectroscopy, electron paramagnetic resonance spectroscopy, small angle X-ray and dynamic light scattering, optical and magnetic tweezers, atomic force microscopy, fluorescence resonance energy transfer, analytical ultracentrifugation, and cryoelectron microscopy. Besides these core courses, the trainees choose from a large panel of electives including a variety of basic and advanced topics in biology, chemistry, and physics or at the interface of these disciplines with the ultimate goal of satisfying the coursework requirements of both their parent graduate program and our molecular biophysics training program.

CREATING AND SUSTAINING INTEREST

Another major challenge for biophysics training programs is in creating and sustaining interest and appreciation for both the biology and the physics ends of the spectrum. There is broad consensus that this can be achieved by highlighting well-developed “case studies” in which a truly important conceptual breakthrough required the unique perspectives afforded by each of these disciplines. This has been a topic of considerable discussion among those most closely associated with our program and a future course offering is likely to formally incorporate this feature. To some extent, this is already being done at the subconscious level in a variety of contexts, including, but not limited to, courses that explore current topics in biophysics and structural biology, biophysics seminars, and journal clubs. Besides the student-run journal clubs, two separate monthly seminar series, one featuring external speakers from around the world and the other featuring Northwestern students and faculty, constitute important mechanisms for intellectual stimulation and engagement. These activities are actively and vigorously pursued by the training program during the school year, and help foster a sense of community and identity for our students and faculty.

CONCLUDING REMARKS

The field of molecular biophysics has been dynamic over the years with the continual emergence of new technologies and opportunities for exciting discoveries. The future promises to be even more exciting as, for example, we obtain detailed pictures of molecules of ever-expanding size and complexity using tools such as crystallography and cryoelectron microscopy on the one hand, and of subcellular features using functional MRI and microscopy on the other. We envision greater integration of such technologies and subdisciplines. Computational sciences, which have remained a largely peripheral discipline of biophysics thus far, are expected to become mainstream and have a profound impact in this integration. There will be a need for future biophysicists to acquire mastery over multiple, diverse approaches to harness their potential. Training programs have to rise to this challenge to address the dual demands of increased courses offerings and content. Much of this will rely on the continual acquisition of appropriate expertise but with one constant—faculty commitment to student training. It is also important that we continue to solicit and receive feedback from our most valuable resource and our future replacements—our student trainees—and act suitably on this feedback to enhance their learning experience.