Exploring the boom and bust of metabolic functional gains and decay in evolving holobionts


   Department of Life Sciences

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  Dr Peter Graystock, Prof Marc-Emmanuel Dumas  No more applications being accepted  Funded PhD Project (UK Students Only)

About the Project

How accurately can we predict and direct the evolution of key metabolic functions within a holobiont? Directed evolution assays are becoming increasingly popular but we still lack a fundamental understanding of the evolution of functional dynamics. Though often thought of as a single species strain mutating over time to another species/strain, the reality in most scenarios is likely to be a transition from a homogenous population of one strain descending to a diversity of strains where new, competitive strains arise whilst the less competitive strains are knocked down1-2. Stable environments may facilitate a low diversity but, the boom and bust of strains over time will be contingent on their functional competitiveness in the environment3. Maintaining less competitive strains in a population may provide a functional and metabolic redundancy, facilitating rapid adaptation in changing environments. This dynamic is poorly understood which presents a challenge to recent advances in the field of microbiome engineering and host-microbe interactions. How persistent will a key microbe be when the selection pressure they co-evolved with is removed? How does the microbial diversity influence the evolutionary optimisation towards a stressor, and once a stressor is removed, how fast will metabolic functionality persist before it decays and is lost from the population? Understanding the evolutionary dynamics of these functional gains and losses will advance not just our general understanding of microbial evolution but also the longevity of microbial applications to combat emerging threats. 

Stressors used in this project will include exposure to cadmium; globally, cadmium (Cd) is major pollutant known to be harmful to a range of organisms from plants and insects to birds and humans at relatively low concentrations ~0.001–1 mg/L. Due to the emerging evidence of cadmium exposure and harmful effects on pollinators4, the experiment will explore core pollinator microbes which have also been shown to have the potential to respond and bioaccumulate Cd3-5. To explore this question, the student will evolve microbial communities to fluctuating stressors using state-of-the-art automated bioreactors and within bees - their usual host/holobiont environments.

Specifically, the student will explore the following;

  1. Evolution: Directed evolution of single and mixed microbe consortia in both automated bioreactors and within bee guts. Regularly collected microbial isolates will be cryopreserved, and growth curves performed against wildtypes to track functional tolerance/utilisation of Cd. Once this stabilises, the selection pressure will be removed allowing the student to track the functional decay over generations with in-depth characterization of their metabolome.
  2. Competitiveness: Using strains of the optimised microbes generated halfway through objective 1, mixed with the wildtype strains from the beginning, the student will track the functional competitiveness (and decay) of the strains over generations in bioreactors and in their bee hosts.
  3. Strain dynamics: Sequencing samples of the microbes collected at regular intervals during the initial optimisation and then during decay at a strain level of resolution; the student will quantify strain level dynamics of competition, dominance, persistence, and extinction.
  4. Strain function: Exploring the metabolic activity and temporal dynamics across the samples collected will identify key metabolic pathways linked to the function6,7 allowing the student to explore their generality across the varying microbial contexts (evolved isolate/consortia/wildtype-mix).
  5. Functional trade-offs: having evolved microbes to one stressor, they will then be exposed to a different category of stressor to explore the presence of functional trade-offs both within their bee hosts and in automated bioreactors.

The student would join the Leverhulme Centre for the Holobiont (www.imperial.ac.uk/holobiont/), a multi-institutional research centre devoted to understanding interactions between multicellular hosts and their microbial symbionts.

Informal enquiries are welcomed and should be sent to Dr Peter Graystock ([Email Address Removed])

How to apply:

Please email Dr Peter Graystock ([Email Address Removed]) and include in your application:

  •    Cover letter
  •    Your CV
  •    Contact details of two referees.

Full applications made before 15th January will be considered at any time.

Funding and eligibility:

A fully funded 4 years Leverhulme Studentship, including tuition fees and a standard research council stipend. The fees and stipend cover UK home applicants and standard research council eligibility criteria apply:

https://www.ukri.org/what-we-offer/developing-people-and-skills/find-studentships-and-doctoral-training/get-a-studentship-to-fund-your-doctorate/

The successful applicant must hold, or be expected to complete, an MSc/MRes with merit/distinction in a relevant subject area of biology, microbiology, ecology, or metabolomics.


Biological Sciences (4) Environmental Sciences (13)

References

1. Turner, C. B., Blount, Z. D., Mitchell, D. H. & Lenski, R. E. Evolution of a cross-feeding interaction following a key innovation in a long-term evolution experiment with Escherichia coli. Microbiology 169, 001390 (2023).
2. Yilmaz, B. et al. Long-term evolution and short-term adaptation of microbiota strains and sub-strains in mice. Cell Host Microbe 29, 650-663.e9 (2021).
3. Rothman, J. A., Leger, L., Kirkwood, J. S. & McFrederick, Q. S. Cadmium and selenate exposure affects the honey bee microbiome and metabolome, and bee-associated bacteria show potential for bioaccumulation. Appl. Environ. Microbiol. 85, 1–18 (2019).
4. Rothman JA, Russell KA, Leger L, et al., 2020, The direct and indirect effects of environmental toxicants on the health of bumblebees and their microbiomes, Proceedings of the Royal Society B-biological Sciences
5. Rothman JA, Leger L, Graystock P, et al., 2019, The bumble bee microbiome increases survival of bees exposed to selenate toxicity, Environmental microbiology
6. Puig-Castellvi F, Pacheco-Tapia R, Deslande M, et al., 2023, Advances in the integration of metabolomics and metagenomics for human gut microbiome and their clinical applications, TRAC-Trends in Analytical Chemistry, Vol:167, ISSN:0165-9936
7. Fromentin, S., Forslund, S.K., Chechi, K. et al. Microbiome and metabolome features of the cardiometabolic disease spectrum. Nat Med 28, 303–314 (2022). https://doi.org/10.1038/s41591-022-01688-4
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 About the Project