The concept of quinary interactions as an organizing principle in cells is receiving renewed attention as researchers in the physical and chemical sciences begin to tackle increasingly molecular aspects of biological complexity. This workshop will explore and discuss the continuum of complexity as the molecular sciences moves from studying single proteins and molecular machines in dilute, in vitro systems, to crowded in vitro systems, to cells. Discussion of experimental, theoretical, and computational approaches at each scale will be mixed with discussion of applications where, ideally, a single system of biological interest has been studied at different scales of complexity using a multiplicity of methods. We aim to identify and promote the intensive discussion of current challenges in this field, with the goal to brainstorm about innovative new methods to measure and model quinary interactions with molecular resolution in realistic environments.
More specifically, we intend to discuss three general conceptual themes, which will be discussed with concrete biological examples including ribosomal stalling dynamics, capturing weak protein interactions, and phase separation in cells:
- Machinery in the cell covers a size range from more dissipative to more mechanical systems. Entropy-enthalpy compensation often defines the properties of such machinery, producing low free energy barriers that make the machinery operable while still rising above background noise. Paradigms from mechanical levers to diffusion-controlled networks, and everything in-between can be used to describe this machinery.
- While engineers generally assemble machinery permanently, the cell often has more transient solutions. Quinary structure binds proteins or RNAs transiently and weakly for functional purposes, whereas quaternary structure is more robust. Liquid phase separation compartmentalizes molecules without membrane boundaries, but one has to wonder why not everything phase-separates in as complex a mixture as the cytoplasm. Spliceosomes undergo extensive assembly and disassembly every time they are needed, being more of a "toolkit" than a solid machine like the ribosome. How does Nature utilize the full spectrum from strongly to weakly assembled components?
- Cell fitness is foremost about survival, not efficiency. While many cellular processes operate close to the thermodynamic limit and are thus "efficient," others are accidents of evolution, or they appear unnecessarily complex on the surface until one asks how cells become so robust. In human-engineered systems, robustness is usually a consequence of making each part highly resilient, but removal of a single part causes malfunction; in cellular systems, most parts can be removed without causing the overall machinery to collapse, even though the occasional part, like a very strong protein-protein interaction, is also highly resilient.
The registration fee includes breakfast on each workshop day. There is also a catered picnic on Wednesday night.
We wish to ensure an intimate workshop setting, with no more than 20 to 25 participants. If you are interested in attending, but have not received an invitation, please contact the workshop organizer before registering. If you have registered for a meeting you were not invited to, you may be subject to a $100 fee.
TSRC is about expanding the frontiers of science, exploring new ideas, and building collaborations. The workshop schedule will allow for substantial unstructured time for participants to talk and think. All participants are expected to stay for the entire duration of the workshop. Scientists are encouraged to consider bringing family or friends. Telluride offers a number of options for children's camps (including Telluride Academy, Ah Haa School for the Arts, and Pinhead Institute). There is more information on childcare, camps, and family activities on TSRC's website at https://www.telluridescience.org/travel/families. Please contact Cindy Fusting at firstname.lastname@example.org for more information.
Telluride Intermediate School
725 West Colorado Ave Telluride, CO 81435