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Optimization and historical contingency in living systems: a biophysical approach

Objective

Populations of living organisms are pushed to optimality by evolution, but may also be shaped by the contingency of their evolutionary history. The recent explosion of sequence data gives us access to the outcomes of molecular evolution, and controlled microbial evolution experiments allow us to analyze the predictability of evolution. In this exciting context, I aim to explore quantitatively the importance of optimization and contingency both at the molecular scale and at the scale of populations of microorganisms, using a theoretical biophysical approach.

First, I will assess how functional optimization and evolutionary history, i.e. phylogeny, shape protein sequences. Importantly, correlations arising from phylogeny are a double-edged sword, often confounding signal from functional optimization, but sometimes providing useful complementary information. I will improve sequence-based predictions for protein-protein interactions by exploiting information both from phylogeny and from the required complementarity of interacting residues. I will disentangle the collective modes of correlations in protein sequences due to optimization from those due to phylogeny, and investigate the importance of functional sectors as an organizing principle of proteins. This will be a breakthrough in our understanding of the sequence-function relationship of proteins.

Second, I will analyze the impact of optimization and contingency on the evolution of microbial populations. I will study microorganisms with a rugged fitness landscape presenting several optima. In these realistic cases, populations tend to remain trapped in local optima. However, most real populations possess specific geographic structures. I will quantitatively study how structure helps populations to explore model and real rugged fitness landscapes. I will build a universal model of structured populations. I will then focus on important applications to antimicrobial resistance evolution and to expanding populations.

Fields of science (EuroSciVoc)

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Keywords

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Programme(s)

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Topic(s)

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Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

ERC-STG - Starting Grant

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Call for proposal

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(opens in new window) ERC-2019-STG

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Host institution

ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 498 214,00
Address
BATIMENT CE 3316 STATION 1
1015 LAUSANNE
Switzerland

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Region
Schweiz/Suisse/Svizzera Région lémanique Vaud
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 498 214,00

Beneficiaries (1)

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