IAP-24-089

Population-scale impacts of metals on microbial communities

Life exists in intermediate, “optimal” regimes. All living organisms need resources (water, oxygen, nutrients, etc.) to grow, but die from toxicity if these resources are supplied too high. Living organisms also coexist in complex ecosystems (e.g., animal gut microbiomes, ponds, forests) that continually evolve. What happens to an ecosystem if a substrate becomes limiting or overabundant? What if a critical species is lost? What if a new species invades?
There are accumulating reports on the effects of metal malnutrition and toxicity on diverse microbial ecosystems (human, animal, plant, environmental). A mathematical model is now needed to extract biological insights. This project will thus combine microbiology and mathematical ecology approaches to understand metals’ impact on microbial communities in diverse ecosystems.

The student will assess the impact of varying metal concentrations on the growth of single-species bacterial cultures and, subsequently, multi-species bacterial communities. The experimental results will be used to iteratively develop a new mathematical model and theory explaining how different bacteria grow and die in response to “toxic nutrients” such as metals and how these responses influence co-existence in more complex bacterial ecosystems.

The student will work in Supervisor 1’s laboratory at Durham to study a model bacterial species. The student will produce five transgenic variants with altered metal-dependent traits (impaired or enhanced in cellular processes such as metal sensing, uptake, export, utilisation, and storage). The student will use high-throughput biochemical approaches to assess bacterial growth and expression of metal-dependent genes.

The student will also gain skills in mathematical modelling of their experimental data via collaboration with Supervisors 3 and 4 at Durham. However, metals can affect bacterial metabolism and, thus, the modelling. Metabolic interactions in bacterial communities can also influence bacterial growth (bacterial cross-feeding, warfare, competition, cooperation). The student will thus use omics techniques to interrogate these via collaboration with Supervisor 2 at Newcastle.

Year 1

– Become familiar with background literature on coexistence theory and metals in biology.
– Gain proficiency in the experimental protocols in Supervisor 1’s laboratory.
– Produce 5 transgenic variants of the model bacterial species.
– Carry out of single-species experiments.
– Begin modelling single-species responses.

Training, particularly in the project’s interdisciplinary aspects, will be crucial in the first few months. Joint meetings and integration within Durham’s Biophysical Sciences Institute will facilitate this.

Year 2

– Continue with single-species experiments.
– Continue with modelling single-species responses.
– Present their work at a local conference or symposium
– Begin constructing multi-species communities.

Year 3

– Complete experimental work and modelling with single-species.
– Continue experimental work with multi-species communities.
– Begin modelling multi-species responses.
– Collect and analyse samples using metabolomics.
– Prepare thesis outline.

Year 3.5

– Complete experimental work and modelling with multi-species.
– Present their work at a more major conference.
– Thesis writing.
– Prepare work for publication.

This project presents a unique opportunity for the student to receive cross- and inter-disciplinary training. In addition to fundamental concepts and techniques in experimental microbiology, the student will also gain knowledge of mathematical ecology and computational models, particularly how they can be applied to guide, understand, and enhance experimental investigations. The student will also gain skills in working with cutting-edge, high-throughput omics data and analyses.

The student will acquire transferable skills, including time management, experimental planning, hypothesis generation, data interpretation, and statistical analyses. They will develop their communication skills by participating and contributing to weekly meetings with Supervisor 1’s group (currently 4 PGRs) and additional regular meetings with the broader supervisory team. These broader interactions will expose the student to different ways of working and help them build their collaboration skills. The student will also build networking skills by attending and presenting at conferences.

The student will enter a vibrant research environment at Durham. Supervisor 1 is in the Biosciences, which hosts biochemists and microbiologists alongside ecologists, providing the student with additional opportunities to explore and apply their interests beyond the specific project topic. The Mathematics-Biology interface is also an emerging strength at Durham. The collaborations between Supervisors 1, 3, and 4 are already ongoing, so the student will be able to hit the ground running. The collaboration with Supervisor 2 is new and brings critical capabilities in metabolomics that are not available at Durham.