The generality, mechanism, and function of bet-hedging in bacteria

Objective

Gene circuits exhibit fluctuations (‘noise’) in the levels of key components such as regulatory proteins. Increasingly, noise appears to play functional roles, e.g it can enable a subpopulation of cells to enter a transient antibiotic-resistant state, enhancing their survival. By ensuring that cells do not all exist in the same transcriptional state, the colony can ‘bet-hedge’ against future environmental changes.

Studying bet-hedging is critical to our understanding of how bacterial gene circuits have evolved in an ever changing and hostile environment. It is also important for public health. The spread of infectious diseases can depend on activation of alternative genetic programs, such as competence, general stress response, and antibiotic persistence in bacteria. I seek to understand the mechanisms by which cells enter these alternate states.

Previous gene expression assays used bulk averages over thousands of cells, causing individual cell behaviour to be lost. I will develop new approaches to attack this problem. I will use single-cell time-lapse microscopy to examine the generality of bet-hedging (Aim 1). I will construct and screen reporter strains for ~120 key pathways in B. subtilis. After screening for pathways that show variable gene expression, I will use synthetic biology and mathematical modelling techniques to discover the gene circuit mechanisms that allow cells to probabilistically enter these alternative states (Aim 2).

In order to test the function of the variable gene expression observed in our reporter strain for each candidate gene I will test whether, upon addition of antibiotics or other stresses, cells that are highly expressing the candidate protein survive or grow faster than cells that are not. I will do this using a novel microfluidic device (Aim 3). This work will lead to a comprehensive understanding of how and why alternative transcriptional states are generated in bacteria.

Fields of science (EuroSciVoc)

CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.

• natural sciences biological sciences microbiology bacteriology
• natural sciences biological sciences synthetic biology
• natural sciences biological sciences biochemistry biomolecules proteins
• natural sciences physical sciences optics microscopy
• natural sciences mathematics applied mathematics mathematical model

Programme(s)

Multi-annual funding programmes that define the EU’s priorities for research and innovation.

• FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)

Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

• FP7-PEOPLE-2012-CIG - Marie-Curie Action: "Career Integration Grants"

Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

FP7-PEOPLE-2012-CIG
See other projects for this call

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.

MC-CIG - Support for training and career development of researcher (CIG)

Coordinator