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Developing next-generation genetic reporters for detecting horizontal gene transfer

Project description

Inside the black box of horizontal gene transfer

Horizontal gene transfer – the non-sexual movement of genetic material between separate organisms – is a primary driver of antibiotic resistance and it is poorly understood. Current experimental methods can only detect completed transfer events, so predictive mathematical models cannot incorporate the fleeting intermediate processes that shape overall dynamics. With the support of the Marie Skłodowska-Curie Actions programme, the SCRIPT project will develop next-generation genetic reporters capable of detecting these transient processes at single-cell resolution to inform predictive mathematical models. Integrating synthetic biology, environmental microbiology and modelling, SCRIPT will shed light on previously inaccessible processes shaping the ecological dynamics of mobile genetic elements while potentially informing targeted strategies to mitigate antibiotic resistance.

Objective

Accurately predicting the spread of genes in the environment via horizontal gene transfer (HGT) is of critical importance to many societal challenges, such as the antibiotic resistance crisis. Our ability to make effective predictions of environmental HGT dynamics is held back by two key knowledge gaps. First, current methods of measuring HGT cannot detect the transient processes that give rise to HGT dynamics, as they can only detect the end result of successful HGT events. Second, mathematical models for HGT spread do not explicitly incorporate these transient processes, limiting our understanding of exactly how these processes affect the spread and mitigation of mobile genetic elements.

In this project, SCRIPT: SynthetiC Recombinase-based Investigation of Plasmid Transfer, I propose to resolve these knowledge gaps by (1) developing the first set of next-generation genetic reporters that can reliably detect target transient HGT processes at high-throughput, single-cell resolution, and (2) incorporating these processes into mathematical models of HGT and using these updated models to quantify the extent to which these measurements enhance model predictiveness of HGT spread dynamics and mitigation strategies. This project is an interdisciplinary effort that combines techniques from synthetic biology and mathematical modeling with those from environmental microbiology and HGT research.

The outcomes of this project will constitute a major advance in the field of HGT research by enabling the measurement of previously- undetectable processes that are critical in shaping the ecological dynamics of mobile genetic elements. The project will also make an important contribution towards enabling the reliable prediction of the environmental spread of mobile genetic elements carrying antibiotic resistance genes, which will inform targeted strategies to mitigate their spread.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

(opens in new window) HORIZON-MSCA-2025-PF

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Coordinator

KOBENHAVNS UNIVERSITET
Net EU contribution
€ 263 393,28
Address
NORREGADE 10
1165 KOBENHAVN
Denmark
Region
Danmark Hovedstaden Byen København
Activity type
Higher or Secondary Education Establishments
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Total cost
No data

Partners (1)