A Quantitative and Systems Biology that fits UC Merced

Quantitative and Systems Biology (QSB) is a foundational idea of UC Merced around which many research groups and organizations on campus have organized and invested. UC Merced’s original and foundational interdisciplinary idea of QSB as a strategic research theme fits well with our scientific age in the ‘century of biology’ [Venter and Cohen (2004) New Perspectives Quarterly 21(4):73]. It also responds adroitly to the National Research Council‘s recommendations for biological research and education in the 21^st Century (http://www.ncbi.nlm.nih.gov/books/NBK32500/ and http://www.nap.edu/openbook.php?isbn=0309085357). With such an auspicious start, QSB helped build UC Merced’s largest graduate and undergraduate programs. That is why QSB should, with renewed purpose and bold leadership, transition from an umbrella for research in the life sciences into a revitalized graduate program and, by 2020, a QSBI ORU and QSB Department, around a unique brand of interdisciplinary, quantitative and systems biology for UC Merced. The strategy outlined below charts a path to renewal and sharpening of a bold mission and vision for QSB that is inclusive, transparent, enabling and facilitates new growth and collaboration without being all things to everybody. UC Merced can rally behind QSB’s renewed mission, by adding quantitative and systems biology as a strategic research theme In UC Merced’s Strategic Academic Vision. By rallying behind QSB’s renewed mission, UC Merced can drive cutting-edge, interdisciplinary innovation and accelerate biological discovery in highly diverse areas of application that matter to UC Merced faculty, the community, and beyond.

The Future of Biology 

Over the years, key investments made in quantitative, systems, interdisciplinary and integrative biology at UC Merced have been rewarded with concrete successes in publications, patents and grants. Examples include the NSF-funded Undergraduate Research Mentorship (URM) program in Computational Biology, a recent NSF INSPIRE award and a recent systems biological NIH R01 award. Yet UC Merced has fallen behind other institutions in building interdisciplinary, quantitative and systems-oriented biology despite that this is the widely recognized future direction of biological research, and that UC Merced possesses unique structural advantages to lead in those areas.

Enabling Biology through QSB

To maximally capitalize on current investments, UC Merced biology must define an interdisciplinary group of affiliated QSB faculty who support its renewed mission, and additionally expand its core QSB faculty who demonstrate the application of inter- and transdisciplinary QSB approaches to biological problems both individually and in collaborative teams (for more on transdisciplinary science please see e.g. [Gray (2008) Enhancing Transdisciplinary Research Through Collaborative Leadership. Am J Prev Med. 2008 35(2 Suppl): S124–S132]). Newly hired core QSB faculty proposed below may work on different biological systems and questions, but they will all share common motivations, approaches and methods to address the information, organization and dynamics of biological systems in general. In order to hire these future transdisciplinary core QSB faculty, QSB will assemble interdisciplinary QSB search committees. This will help ensure the hiring of core QSB faculty who actively and intrinsically promote interdisciplinary research not only through collaboration, but individually.

A Revamped QSB Mission

The proposed future mission statement for QSB is “to accelerate discovery of basic biological principles through interdisciplinary innovations in high-dimensional, multi-scale observations and simulations of living systems, high-performance computational science, and theory with a focus on information, organization, dynamics and emergent properties of biological systems across spatiotemporal scales.”

QSB’s Grand Challenge
The grand challenge QSB will address is to fully explain and predict the organization and dynamics of living systems. Why does life happen in the universe? How do system-level properties like robustness, plasticity, adaptation and cooperation emerge from the dynamics of smaller entities?  To answer these questions, we must study the organization and flow of information in biological systems.

QSB 2020: QSBI and a Department of Quantitative and Systems Biology for UC Merced

By 2020 QSB proposes to establish the Quantitative and Systems Biology Institute (QSBI) as an ORU to  manage campus-wide partnerships in furtherance of its mission. For example, QSBI will synergize activities with other graduate groups, HSRI, SNRI, ERI, the Center for Statistical and Quantitative Research (CeQR), the newly proposed Center for Human Adaptative Systems and Environments ORU (CHASE) and the newly proposed Center for Theory and Computation CRU (CTC). QSBI will support interdisciplinary research consortia with QSB affiliate faculty in SoE and SSHA for initiatives like complex systems neuroscience, strengthening a key strategic area shared between QSB and the Cognitive Sciences unit. Additionally, QSBI will manage relationships with state, federal and private entities vested in UC Merced’s quantitative and systems biology programs. Candidate partners include QB3 and biotech companies, Contract Research Organizations and biotech incubators, fostering extramural public-private partnerships and capital investments on campus. In addition, by 2020, a UC Merced Department of Quantitative and Systems Biology will serve current and growing demand for interdisciplinary undergraduate education in quantitative and systems biology. This supports the UC Merced Mission to mesh graduate and research programs with high-quality undergraduate programs and interdisciplinary research as a nourishing foundation for undergraduate learning. 

Getting to QSB 2020

In Phase I (completed AY13-14), a renewed QSB mission must be negotiated to lead this effort with all UC Merced faculty who support it. QSB further needs reorganization into core and affiliated QSB faculty in seven different emphasis areas. Affiliated faculty will be asked to pledge their support to this renewed QSB Mission in exchange for membership benefits including the training and support of QSB students. Affiliated QSB faculty need not conduct exclusively QSB-style research in order to affiliate with QSB or gain its benefits. On the other hand, core QSB faculty commit to building QSB directly through QSB research, teaching and service. The renewed mission and organization of QSB will be defined through a dialogue of interested faculty parties during Phase I in a transparent, accessible and fully accountable process.

In Phase II (starting AY14-15), QSB will lead hiring of additional core QSB faculty. QSB will court campus partnerships and extramural strategic capital investment and funding around its core Mission.

In Phase III (starting AY15-16), QSB will propose a Quantitative Science Biology Institute ORU and lay foundations to create an interdisciplinary Department of Quantitative and Systems Biology with degree programs for undergraduates.

The Core QSB Program. QSB will be organized into seven proposed emphasis areas of 1) molecular systems biology (including macromolecular systems and metabolomics), 2) cellular and developmental systems biology (including cellular networks, systems neuroscience, systems immunology and developmental systems biology), 3) microbial systems biology, 4) organismal and integrative systems biology (including systems physiology), 5) systems ecology (http://www.nature.com/news/systems-ecology-biology-on-the-high-seas-1.13665), 6) quantitative and theoretical biology and 7) synthetic biology.  Through these emphasis areas, QSB will also address problems in astrobiology, biomedicine, and environmental science thereby contributing to many of the core research themes in UC Merced's Strategic Vision. In Table 1, all current QSB faculty are listed by an estimated best fit to one or more of these seven emphasis areas of QSB. Many faculty fit more areas than listed.

What We Need to Attain QSB 2020

1. Adoption of QSB strategic theme, flexible graduate programming, and liberation from ‘umbrella’ status.

UC Merced should make Quantitative and Systems Biology a strategic research theme in its Strategic Academic Vision. Internally, refocusing and sharpening its identity around a renewed mission and vision will be a dynamic process for QSB that cannot be expected to emerge by strict consensus among all its current members. Therefore, most immediately, QSB needs the approval of additional graduate programs in life sciences at UC Merced to accommodate faculty for whom QSB does not express their highest research priorities. Outside QSB, We should not tie the future of the campus to existing administrative units in fear of spreading resources too thin. Different biology units serve different markets for funding dollars as well as student and employer demands. Although health and biomedical research is now strongly served, the growing demand for biologist-programmers and interdisciplinarily and quantitatively trained biology students will be better served by the QSB of tomorrow. By diversifying and sharpening its biology portfolio, UC Merced will gain more students and more dollars. By providing flexibility for faculty to self-organize around diverse missions UC Merced can make room for a renewed QSB as described here.

Table 1. Current QSB Faculty by Potential Primary Emphasis Area of Systems/Synthetic Biology

2. Core FTEs in QSB.  QSB needs core QSB faculty who will commit to building QSB directly through QSB research, teaching and service. The research programs of these core faculty need to be intrinsically interdisciplinary, quantitative and systems-oriented, yet address diverse basic science questions in biology. QSB itself needs to oversee the hiring of core QSB faculty committed to interdisciplinary science, quantitative methods, big data approaches, and basic science in each of its seven areas. The identification of a home bylaw unit for core QSB faculty recruits is secondary and can potentially occur late in the recruitment process. Table 2 below shows a suggested plan of QSB recruitment to 2020.

3. An intrinsically interdisciplinary department. QSB should form UC Merced's first intrinsically interdisciplinary department in science and engineering at UC Merced. A QSB department will meet the challenges and fulfill the potential of our outstanding undergraduate population by carefully designing a challenging, interdisciplinary approach to biology education with a strong and consistent emphasis on programming and modern statistics, integrative biology, bioinformatics, biochemistry, biomathematics and biophysics. A QSB department can oversee hiring and promotion of transdisciplinary QSB core faculty who may not be as easily evaluated and mentored in disciplinary bylaw units. Departments do not yet exist at UC Merced. They could be defined flexibly to be just bylaw units, or something different. Either way, an administrative structure must be created to reward participating faculty and units for fulfilling QSB undergraduate and graduate teaching needs and carrying out hiring and promotion in its service. An undergraduate major in quantitative and systems biology will meet future job market demands, help relieve MCB of some of the burden of teaching the BIO major, and increase the competitive of UC Merced undergraduates for future biological careers.

Table 2. Proposed QSB Core Faculty Hires by AY, Corresponding Emphasis Areas and Collaborative Beneficiaries (“dry lab” hires are shown in italics)

CHASE: proposed Center for Human Adaptive Systems and Environments ORU.

CTC: proposed Center for Theory and Computation CRU.

CeQR: Center for Statistical and Quantitative Research

ERI: Energy Sciences Institute

CIS: Cognitive and Information Sciences

4. An affiliated ORU in systems biology to cultivate partnerships with state agencies, federal funding agencies and companies for capital investments.  It is a goal for QSB to strengthen and focus the existing QSB program into a Quantitative Systems Biology Institute ORU, QSBI.  QB3 Director Regis Kelly expressed interest in extending QB3 benefits to UC Merced as part of an extended  “QB North Consortium” — this would provide resources for individual faculty to transfer technology related to systems and synthetic biology to biotechnology and other companies. As industry relationships strengthen through the hiring of core QSB faculty such as Clarissa Nobile (hired into MCB AY 12-13 who has started a biotech company through QB3), QSB can cultivate private investment for buildings, instrumentation and other resources.Space needs of the future QSB units to be procured through public-private partnerships include co-located space in a dedicated building for core QSB faculty, core facilities for high-throughput data generation and computation, and a conference-scale auditorium.
 

Metrics of Success

QSB metrics of success will include 1) the attainment of extramural funding to build interdisciplinary QSB-style graduate and undergraduate degree programs through training grants, 2) improvement in merits of student applicants to QSB programs, 3) the breadth (diversity) and volume of extramural grants, publications and intellectual property enabled by QSB core faculty, QSB-funded students, and QSB research infrastructure, and 4) public-private partnerships for fellowships and capital investment to build core QSB research infrastructure.

Aligned and Aspirational National and International Programs Comparable to QSB
Aligned systems biology institutes to QSBI would include Yale Systems Biology Institute, Systems Biology Center New York, other NIGMS-supported National Centers for Systems Biology (http://www.systemscenters.org), and BBSRC Integrative Systems Biology Research Centres in the UK. Aligned undergraduate programs would include Computational and Systems Biology at UCLA and MIT, Department of Cell and Systems Biology at U Toronto, and a Systems Biology at CWRU. Examples of aspirational programs include the FAS Center for Systems Biology at Harvard.

Undergraduate Learning in Quantitative and Systems Biology

There is pent-up demand for undergraduate training in computational and systems biology at UC Merced. Informally from a poll this semester in BIO 2, about 10% of Bio majors are hobby programmers potentially interested in computational biology. But this is probably an underestimate, as today's quantitatively-minded students choose other programs besides the BIO major including Bioengineering and the quantitative biology emphasis in Math. Examples of model future QSB students include Sophomore Bio 2 student Forrest Yeh who took the initiative to 3D-print the structure of yeast invertase enzyme in the Mechatronics lab after hearing about its role in the 2013 Nobel Prize in Physiology and Medicine to Randy Schekman, and Bioengineering 4th year Claudia Canales who will submit an abstract in January on her QSB research at Stanford's Biomedical Computation Conference ( http://bcats.stanford.edu/html/home.html ). Also UC Merced has, since 2012, fielded teams to iGEM (http://igem.org/) even without a campus unit for synthetic biology. With its proximity to world-leading tech industries, a QSB major would create new opportunities for our student population and drive a unique recruiting brand for UC Merced.