A Short Course in

Systems Biology - Foundations

The Systems Biology - Foundations course is a two- or four-week didactic and practical educational experience which begins with an initial two-week online workshop devoted to filling gaps in knowledge in understanding in both "wet" and "dry" disciplinary backgrounds and presenting select topics as examples of a need for interdisciplinary approaches to solving biological problems, followed by a two-week in-person course of lecture and laboratory modules including activities focused on the teaching of collaborative skills and career development.

Who Should Apply?

This program is targeted at graduate students, post-docs, faculty and industry researchers with either of two backgrounds: training mainly in experimental biology (e.g. molecular biology, cell biology, genetics, biochemistry, physiology, etc.), or training mainly in mathematics, physics, engineering or computer science. For short, we like to call these backgrounds “wet” and “dry”, respectively.

Whatever your background, if you are reading this, you’ve probably had some specific experience—in the classroom, library or laboratory—that led you to wonder whether you could have a more effective and more satisfying research experience by reaching across the Wet/Dry divide.

Maybe you are a “Wet” individual who has seen the value of modeling in making biological systems understandable, or you find yourself confronted with a new massive dataset that you sense requires some sophisticated algorithmic or statistical thinking to be fully understood. Or maybe you are a “Dry” individual who senses that your quantitative skills ought to be of great value to biology, but you are unsure of how to apply them in a manner that solves real—and not just toy—problems.

Whatever the reason, and at whatever career stage you may be, some of the issues that are likely to stand in your way are deficits in knowledge (Wets are sometimes very far behind in quantitative skills; Drys sometimes have had only very superficial contact with real biological systems); language barriers; institutional training structures that hinder taking courses outside your discipline; fellowship funding mechanisms that favor uni-disciplinarity; and a lack of interdisciplinary role models available for mentoring. This course seeks to address each of these issues, through skills training, network building, and mentoring that continues beyond the three weeks you spend in the course itself.

Read on for more information about the course philosophy and the systems biology movement...

Course Philosophy

“Research spirals inward; science cascades outward”. This message, which opened a 2007 article on interdisciplinarity from the National Academies Keck Futures Initiative1, has grown ever more timely, as biological and biomedical science overflow with technology-fueled discoveries, and accumulate virtual mountains of data far faster than analysis can keep up. Methodologies for acquiring and digesting knowledge in biology and medicine now cascade so regularly outward into the domains of physics, mathematics, chemistry, engineering, computer science, statistics, game theory and the social sciences, that interdisciplinarity has become a watchword everywhere that scientists are being trained.

In 2009, the National Research Council (NRC) of the U.S. National Academies of Science and Engineering proclaimed the dawning of an era of “New Biology”, characterized by “re-integration of the many sub-disciplines of biology, and the integration into biology of physicists, chemists, computer scientists, engineers, and mathematicians”2. A subsequent 2014 NRC report on “Convergence: facilitating transdisciplinary integration of life sciences, physical sciences, engineering and beyond”, which stressed the need for “a comprehensive synthetic framework for tackling scientific and societal challenges that exist at the interfaces of multiple fields,” drew heavily on examples from biology and medicine to illustrate promises and challenges associated with interdisciplinarity3. It is perhaps not surprising that, by 2011, the journal Science reported that “30% to 40% of all requests for proposals from the NSF and NIH explicitly required an interdisciplinary approach”4.

Interdisciplinarity has also been highly visible on the international science scene, enough to garner a special issue of Nature highlighting the subject in 2014. That issue included quantitative data5 documenting that interdisciplinarity of publication in the natural sciences and engineering has risen steadily since 1980; that interdisciplinary publications tend to have much greater long-term impact (despite lower short-term impact) than disciplinary ones; and that the life sciences and health sciences are among the areas in which the most interdisciplinary work is being done.

One of the many reasons that have been offered for the global rise of interdisciplinarity in the sciences is the increasing focusing of research on complex, real-world opportunities and problems, which tend not to fall neatly within academic disciplinary lines6. Yet for all the publications that have championed the potential of interdisciplinary research, at least as many have called attention to the unique hurdles that need to be overcome in implementing it. Challenges exist in the categories of funding, education, career development, and evaluation. In this proposal, we focus on challenges in education and professional career development associated with interdisciplinary approaches to biological and biomedical science. In our opinion, the unique history of life sciences professional training in the U.S., which has long tended to emphasize “spiraling in” over “cascading out”, poses barriers to the development of an interdisciplinary workforce, and potentially hinders the career success of trainees attracted to interdisciplinary research. Our motivation in developing this program was to help address the pressing need that this situation has created.

Why Systems Biology?

The term “systems biology” has been applied to a variety of activities that have taken root in biological and biomedical research since about 2000 (although its roots go back much farther). Hallmarks of the systems biology approach include mathematical modeling; the application of engineering and control theory; the analysis and visualization of “big data”; the use of physics methodologies to understand “emergent properties”; the development and application of bioinformatics tools; and the promotion of synthetic biology as a research tool. Concepts in systems biology go beyond the search for cellular and molecular mechanisms, and include the elucidation of dynamics, self-organization, robustness and design.

Not truly a subfield of biology—since it considers every aspect of biology within its purview—systems biology is probably best understood as a “movement”, that is, a concerted effort by researchers and educators to ask and address the questions of life in a way that departs substantially from earlier traditions. At the heart of this movement lies a commitment to tackle the daunting complexity of biology through the embrace of interdisciplinarity. Of course, biology is no stranger to cross-fertilization (one need only think of the physicists who helped launch the molecular biology era), but the kind of disciplinary melting pot that systems biologists advocate (and have to some extent achieved) stands apart from anything in the history of biology (and perhaps even the history of science in general). Although they took pains not to use the name explicitly, systems biology is clearly what the NRC was referring to when it laid out plans for a “New Biology” in 20092.

Why UCI?

The Center for Complex Biological Systems (CCBS), started in 2001 as a discussion forum among a dozen faculty from biology, mathematics and engineering, and grew into a thriving community of over 100 laboratories, supported by a variety of external grants. Its mission has been to promote systems biology research and training to foster the development of a closely-knit community of biologists, clinicians, physicists, mathematicians, chemists, engineers and computer scientists. CCBS has organized workshops, symposia, retreats, pilot grant competitions, “focused interest groups”, and directly sponsored research. Since 2007 it has administered an innovative graduate (Ph.D. and M.S.) training program, known as Mathematical, Computational and Systems Biology (MCSB), which admits students with backgrounds in mathematics, physics, computer science, engineering, and chemistry as well as biology.

Creating MCSB gave CCBS faculty experience in devising interdisciplinary courses; teaching and mentoring across disciplinary lines; and finding creative solutions for addressing the unique challenges of training an extremely diverse cohort of students. Experimental approaches, such as pre-entry “bootcamps”; one-on-one tutoring; and the introduction of student-centered interdisciplinary seed grants, were tested, evaluated, and implemented. The success of MCSB led CCBS faculty members to develop, in 2009, a “national short course” providing three intensive weeks of systems biology training focused on the topic of “Morphogenesis and Spatial Dynamics”. Applicants came from universities and companies from around the U.S. and internationally. The course was funded by the NIGMS for a total of six years, concluding with a final session in January 2016. The present course builds upon many of the lessons learned during these six years. It also broadens the training mission to include a broader view of systems biology, and to include substantial post-course mentoring.