Frontiers in Biophysics: Forum 2008.

January 19, 2008, Downtown Vancouver's SFU Harbour Centre

Keynote and Workshops
Other abstracts: Grad Talks, Posters & General Participants

Event Abstract
Keynote Presentation
Functionally Distinct Dynamics in Structurally Homologous Biomolecules
Dr. Melanie O'Neill (SFU Chemistry)

Nature often exploits structurally homologous molecules to perform very distinct functions with high specificity. One mechanism for encoding dissimilar functions within similar tertiary architectures may be to tune dynamic movement at the primary sequence level. This is illustrated with an example from the RNA world: the purine riboswitches. These non-coding RNA molecules are a pair of molecular look-alikes that selectively bind either adenine (ARNA), or guanine (GRNA) in order to regulate transcription of their downstream genes. Mechanistically unlike protein transcription factors, these riboswitches must act while being synthesized by RNA polymerase, and their response may be governed by the path of ligand-mediated folding. Indeed, we find that it is the distribution of the ligand-bound conformers along the RNA folding pathway, not the final folded state, that distinguishes the purine riboswitches. Rather than time-resolving the folding process, we adjust the position of the folding equilibria, and resolve the ensemble distribution of conformers using the fluorescence lifetimes of their bound ligand. Our results reveal that the sequence of the RNA scaffold tunes the conformer energy, and thereby adjusts the balance between ligand-mediated folding and unfolding. We present a model in which the RNA scaffold of GRNA is more preorganized, while that of ARNA is more conformationally flexible. On a molecular level, these differences indicate that residues remote from the binding site sensitively tune ligand-mediated RNA folding. On the functional level, we propose a role for these divergent dynamics in ligand discrimination and gene regulation.
Workshop A
Observing and modeling organelle transport in living cells
Michael Silverman (Biology) & Eric Cytrynbaum (Mathematics)

Michael will discuss why intracellular transport is important and ways in which transport is observed and quantified. Topics will include the role of motor proteins, organelles and their transport, and observing and quantifying transport. The unifying idea is in the context of experimental approaches to studying transport in living cells.

Eric will discuss some of the theoretical issues that arise in properly localizing proteins and organelles in a cell. Recent experimental and modeling work on both in vivo and in vitro assays involving microtubules and their associated motors will be described. An emphasis will be placed on the basic modeling techniques involved.
Workshop B
Programming the fate of cells
Esther Verheyen (Molecular Biology & Biochemistry) & Eldon Emberly (Physics)

Square One: Cell Fate Decision Making In this session we will review the biology of stem cells, highlighting the general principles that govern the development of a cell from an undifferentiated state into a specific tissue. We will also discuss how mathematical modeling can provide insights into the mechanisms that regulate this differentiation process, and the generation of multiple stable cellular states.

Square Two: Stem Cell Therapy and Synthetic Biology: In this session we will discuss some recent work on reprogramming differentiated stem cells into an embryonic state and their use in the treatment of disease. As a follow up we will also discuss a recent review of synthetic biology, which has been touted as a method for being able to program the differentiation of stem cells into the proper tissue.

The Papers:

1) Hanna J, Wernig M, Markoulaki S, Sun CW, Meissner A, Cassady JP, Beard C, Brambrink T, Wu LC, Townes TM, Jaenisch R. Science 318, 1920 (2007). (PDF)

2) Andrianantoandro E, Basu S, Karig D and Weiss R. Mol Sys Bio 2, 2006:0028 (2006). (PDF)
Workshop C
Probing an individual among the masses
Nancy Forde (Physics), John Bechhoefer (Physics), Carl Hansen (Physics), Andre Marziali (Physics) & Hongbin Li (Chemsitry)

In the first part of this workshop, we will be presenting different approaches to analysing the physical properties and responses of single biomolecules and single cells. A brief presentation by each of the panelists will describe techniques for these biophysical experiments as well as the types of questions that have been addressed by these techniques in our labs and elsewhere.

In the second part of this workshop, we seek to address the larger scientific and technological relevance of these approaches. Specifically, we will be moderating a discussion on the topic of Nobel prize-worthy research. We hope for a wide-ranging discussion among the panellists and audience members about what research or development to date in the field of single-molecule / single-cell biophysics has had a significant impact.

* Should a Nobel Prize be awarded for single-molecule or single-cell analysis?

* If so, for what should it be awarded?

* If not, what would it take for the field to get to that point?