Biological science is on the cusp of a new and transformational way to view living systems – the creation of physical molecular models of the fundamental unit of life, the cell. Such an undertaking will lead to an understanding of the continuity of life’s mechanisms from the atom to the organism. Its potential will be in how we can more comprehensively control cellular behavior in sickness and in health, and in transforming cell biology from an observational to a synthetic science.

Several technical and scientific advances have brought us to this inflection point. Structural data from atomic resolution x-ray crystallography and NMR spectroscopy, to electron and light microscopy is now available at a wide range of length scales – ranging from atomic resolution structures of cellular protein and nucleic acid components to organelle and larger cellular structures. Biophysical approaches including fluorescence microscopy and mass spectrometry can now define spatial distributions and dynamics, and expression and concentration levels are obtainable via technologies ranging from chip arrays and other mRNA technologies to proteomic analyses. Complementary to these experimental methods are the bioinformatic and systems biology approaches that describe and analyze molecular interaction networks, signaling pathways and information flow in complex cellular environments. Underpinning all of these advances is the continuing exponential growth of computer power, in parallel with the ability to gather and integrate enormous amounts of experimental data, and to then use that data to drive physical simulations. Computation will play a key role in turning these islands of data into a continuous landscape of interdisciplinary and cross-scale collaborations and knowledge.

While constructing and simulating computational models of an entire human cell are beyond our current capabilities, we are initiating this training program in interdisciplinary research to foster new research and methodologies that will contribute to progress toward this long-term goal. The systems that we envision being studied within these fellowships may include large biological systems such as enveloped viruses, bacteria, large biomolecular assemblies or machines, cellular organelles or non-enveloped cellular complexes, cytoskeleton and other cellular structural elements. Connection to biomedical challenges is strongly encouraged.

We also intend to support the exploration and development of computational framework(s) that allow and enable integration of all kinds and types of relevant biological data streams (e.g., genomic sequences, x-ray crystallography data, microscopy data, HDX-MS data, etc.) into one interoperable context. This may also include development or application of new or emerging mathematical techniques to biological systems of interest, or the development of computational programs / frameworks that provide new scale crossing capabilities.

Collaboration: A specific objective of the program is that fellows should be prepared for research careers in which collaboration and integration across levels of analysis are key elements. Plans for fostering collaborative relationships during the training period should be addressed. The purpose of the dual mentorship nature of this fellowship is to bridge between two different and complementary aspects of cellular structure across scales of space or time and across disciplines. Examples of the kinds of cross disciplinary collaborations that this program wishes to foster are, but not limited to:
• Bridging between computational and experimental biology of cellular components
• Bridging across spatial or temporal scales of structural cellular systems
• Integration of bioinformatic, proteomic or metabolomics data with structural biological data

Fellows will be expected to gain broad research exposure in an area of molecular cell biology and/or neurobiology as well as in an allied discipline not typically associated with these disciplines such as, mathematics, physics, bioengineering, informatics, systems biology, computer science or translational medicine (but not exclusive to these areas). Active mentorship by a primary sponsor/mentor and a co-sponsor/mentor, representing different disciplines or levels of analysis, is required. Fellowship awardees are required to pursue their research training on a full-time basis normally defined as at least 40 hours per week.