THE ROLE OF ENERGY EXPENDITURE IN MOLECULAR INFORMATION PROCESSING
Postdoctoral Research Fellowship at Harvard Medical School
Application deadline: 31 January 2018. THIS POSITION HAS NOW BEEN FILLED.
Applications are invited to work with Professor Jeremy Gunawardena on the above project, funded by the Giovanni Armenise Foundation. The Gunawardena laboratory studies cellular information processing using a combination of experimental, mathematical and computational methods and offers an intellectual space between the mathematical and the biological sciences.
In recent work (PMID 27368104), we put forward the concept of "Hopfield barriers". John Hopfield's classic work on kinetic proofreading (PMID 4530290) can be interpreted as follows: to undertake any information processing task, if the molecular mechanism implementing this task operates at thermodynamic equilibrium, then there is a barrier, which is set by detailed balance, to how well the task can be performed. The only way to exceed this "Hopfield barrier" is to expend energy and maintain the system away from thermodynamic equilibrium, for which kinetic proofreading is one potential mechanism.
We used the linear framework for timescale separation, introduced in earlier work (PMIDs 22606254, 24018536, 24103070, 25475875), to determine the Hopfield barrier for sharpness in gene activation (PMID 27368104). Gene regulation in eukaryotes offers an important context for these ideas and is the subject of a related project in collaboration with Angela DePace's lab.
The present project will use the linear framework to explore biological information processing from the perspective of Hopfield barriers and non-equilibrium physics. What are the Hopfield barriers for different tasks? How can energy be expended to break these barriers and what is gained by doing so? How can departure from thermodynamic equilibrium be detected experimentally? What are the trade-offs in expending energy, for instance, for achieving not just task accuracy but also speed and minimum energy dissipation (q-bio.MN:1710.06038)? Following the energy may be a way to rise above the overwhelming molecular complexity of biological systems and disentangle their evolutionary logic. The development of single-molecule methods and super-resolution microscopy are providing the right kinds of experimental tools for doing this but they need an appropriate theoretical foundation from which to interpret data and design experiments. That is what we hope to provide.
The position is available for two years; an extension beyond that will depend on additional grant funding. Applicants should have a PhD in one of the mathematical and physical sciences, a good track record of creative work, a strong interest in modern biology and an enthusiasm for working at the interface between disciplines. Applications should be sent to jeremy(AT)hms(DOT)harvard(DOT)edu and should include a CV, a cover letter describing suitability for this specific project and contact details for up to three referees. We are an equal opportunity employer and all qualified candidates will receive consideration for the position.
Copies of our papers mentioned above can be found at vcp.med.harvard.edu/papers.
The lab has a tradition of recruiting undergraduate students in the mathematical sciences for summer internships and rotations. Please contact us if you are interested.