Abstract

Molecular machines and motors allow cells to perform different functions by using the energy produced by ATP or GTP hydrolysis. While some proteins, such as the myosins in our muscles, convert ATP energy into mechanical work on their own, other motors require the coordinated action of multiple proteins. For these systems, molecular mechanisms at play are misunderstood because they emerge from complex interaction networks yielding collective behaviors.

This project proposes to develop new tools and methods to address this problem by comparing two model systems. The first model is the assembly of the actin cytoskeleton, which requires several proteins and ATP to sustain efficient force generation over long periods of time. The second model is a molecular oscillator, which uses GTP to promote the spatial activation of motility in bacteria.

Keywords

Dynamic systems, molecular oscillators, ATP and GTP, biophysics, mathematics and computational biology, actin cytoskeleton

Objectives

The objective of this project is to integrate biophysical, mathematical and computational approaches to understand conserved molecular mechanisms in biology. The recruited student will be working in close collaboration with experimentalists, in order to obtain the data necessary for the implementation of its models, and reciprocally to guide the experimentalists towards the development of more efficient reconstituted systems.

Proposed approach (experimental / theoretical / computational)

The student will be working in close interaction with experimentalists.

From the experimentalists, the student will be in charge of collecing information relative to the biochemical and biophysical properties of the proteins at play, in order to complexify progressively the developed models. For the simplest molecular systems, it will be possible to solve sets of differential equations in order to predict the evolution of the systems over time. For more complex situations (in particular for non-markovian processes), it will be necessary to develop more complex in silico tools to predict the stochastic evolution of these systems.

Reciprocally to the experimentalists, the student in charge will be expected to discuss and find ways to test the predictions of its models in the lab. We expect that results from the models will enable us to pregressively reconstitute some of these complex molecular mechanisms in vitro.

Interdisciplinarity

This project provides an opportunity for a curious student to develop skills in biology (by gaining an in-depth understanding of two mechanisms essential to many biological processes), in biophysics (by seeking to understand the physical principles underlying two biological machines, using ATP and GTP as energy sources), in biochemistry (by understanding how multiple individual interactions between molecules of interest are coordinated to perform a desired function), and computer science (in order to propose powerful computational methods and tools to carry out these applications).