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  Assembling Functionally Stable Microbial Communities Under Fluctuating Environments


   Department of Life Sciences

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Prof Samraat Pawar Prof Cleo Kontoravdi Prof Benoit Chachuat Prof Rodrigo Ledesma-Amaro  No more applications being accepted  Competition Funded PhD Project (UK Students Only)

About the Project

Microbes (Prokaryotes and Fungi) play a dominant role in carbon and nutrient cycling globally by decomposing organic matter in aquatic as well as terrestrial ecosystems. Therefore, understanding how microbial communities assemble and function in nature is among the foremost challenges in ecology. However, because these communities are extraordinarily complex with myriad interacting species, our ability to predict their dynamics in the face of natural and human-induced environmental changes (such as climatic warming) is severely limited. The goal of this PhD project is to develop a modelling framework implemented as a software package to predict the assembly and functional stability of microbial communities in fluctuating environments. Some key questions that may be addressed are:

1. What combination of resource competition and cooperation through cross-feeding on metabolic by-products (species interaction structure) guarantee functionally stable communities in a given temperature regime?

2. How does temperature change affect the stability of community-level species interaction structure over time?

3. What species functional capabilities (traits) and interaction structures maximize functional stability in the face of directionally changing or fluctuating environmental temperatures?

The student will take the novel approach of merging AI-assisted genome-scale stoichiometric modeling of microbial metabolic networks (GEMs) with models of consumer-resource dynamics to more accurately capture community dynamics under different resource availability and temperature conditions. The model will be applied to data from laboratory experiments, testing predictions about which microbial strains are likely to coexist in a shared environment based on their functional traits, and the resultant effects on community respiration rate, metabolite production, and population abundances. Respiration quantifies the carbon processing rate of the community and is a crucial factor in ecosystem and global carbon cycles. Metabolite production reflects the functional composition of the community. Total abundance reflects secondary productivity (capture carbon ability) of the community while strain-level abundances and covariances between them reflect how distinct metabolic strategies interact to produce community function. Successfully developing such an integrated, mechanistic modelling framework holds great potential to reveal general ecological rules, and will be a significant step towards predicting the effects of climate change on ecosystem functioning, with applications in ecosystem conservation, restoration and engineering, as well as fundamental microbiome research.

Thus this project will advance the current state-of-the-art of ecological theory through the development of a novel computational model. To this end, it will leverage a combination of theory — on Complex adaptive and ecological systems (Pawar), Metabolic networks (Kontoravdi and Pawar) and biochemical process optimisation (Chachuat) — with empirical data (Laboratory experiments - Ledesma-Amaro). This will result in a uniquely multi-disciplinary PhD research project that combines mathematical theory, computational biology, laboratory experiments, and statistical analyses of empirical data, to address an important and general problem in applied ecology. The project's objectives also contribute strongly to the UL National Environmental Research Council's goal of enabling society to predict and respond to the effects of climate and ecosystem functioning. The student will also receive advanced training in 6 of the 15 “most wanted skills” identified in NERC’s 2012 report: Modelling, Multi-disciplinarity, Data management, Numeracy, Microbiology, and Freshwater Science. The student will learn high-level computing and mathematical modelling skills in the area of Nonlinear Dynamics and Biological Systems & Network theory, and data management and analysis skills training through the empirical parameterization and validation. The complexity of the numerical computational analyses of dynamical networks along with the laboratory data will necessitate development of advanced numeracy skills.

This project is be part of the SSCP DTP program (https://www.imperial.ac.uk/grantham/education/science-and-solutions-for-a-changing-planet-dtp/), and the succesful candidate will join its unique multidisciplinary PhD training programme its multi-year and interdisciplinary cohort of existing students spanning all areas of earth science and environmental research at the College.

How to apply: Please send your CV, contact information for 2 references, and a 1 page statement describing your interest in the project to Samraat ([Email Address Removed] ) by Monday January 08 2024.

Biological Sciences (4) Chemistry (6) Engineering (12)

Funding Notes

The student should qualify for Home Fees in England: Candidates must be either UK or EU nationals with settled status, and resident in the UK for at least 3 years prior to the commencement of the studentship. Please see this for more info: https://www.findaphd.com/guides/research-council-studentships

References

[1] Bar-On, Y. M., Phillips, R. & Milo, R. The biomass distribution on Earth. PNAS 115, 6506–6511 (2018).
[2] Cavicchioli, R. et al. Scientists’ warning to humanity: microorganisms and climate change. Nat Rev Microbiol 17, 569–586 (2019).
[3] Rocca, J. D. et al. The Microbiome Stress Project: Toward a global meta-analysis of environmental stressors and their effects on microbial communities. Front Microbiol 10 (2019).
[4] Thompson, L. R. et al. A communal catalogue reveals Earth’s multiscale microbial diversity. Nature 551, 457–463 (2017).
[5] Smith, T. P. et al. Community-level respiration of prokaryotic microbes may rise with global warming. Nat Comm 10, 5124 (2019).
[6] Smith, T. P., Clegg, T., Bell, T. & Pawar, S. Systematic variation in the temperature dependence of bacterial carbon use efficiency. Ecol Lett 24, 2123–2133 (2021).
[7] Goldford, J. E. et al. Emergent simplicity in microbial community assembly. Science 361, 469–474 (2018).
[8] Machado, D. et al. Polarization of microbial communities between competitive and cooperative metabolism. Nat Ecol Evol 5 (2021).
[9] Sepulveda, J. & Moeller, A. H. The Effects of Temperature on Animal Gut Microbiomes. Front. Microbiol. 11, 384 (2020).
[10] Merino, N. et al. Living at the Extremes: Extremophiles and the Limits of Life in a Planetary Context. Front Microbiol 10 (2019).
[11] Marsland, R. et al. Available energy fluxes drive a transition in the diversity, stability, and functional structure of microbial communities. PLOS Comput. Biol. 15, e1006793 (2019).
[12] García, F. C. et al. The temperature dependence of microbial community respiration is amplified by changes in species interactions. Nat Microbiol 8, 272–283 (2023).
[13] Lechón-Alonso, P., Clegg, T., Cook, J., Smith, T. P. & Pawar, S. The role of competition versus cooperation in microbial community coalescence. PLoS Comput Biol 17, e1009584 (2021).
[14] Cook, J., Pawar, S. & Endres, R. G. Thermodynamic constraints on the assembly and diversity of microbial ecosystems are different near to and far from equilibrium. PLoS Comput Biol 17, e1009643 (2021).
[15] Machado, D., Andrejev, S., Tramontano, M. & Patil, K. R. Fast automated reconstruction of genome-scale metabolic models for microbial species and communities. Nucleic Acids Res. 46, 7542–7553 (2018).
[16] Fahimipour, A. K. & Gross, T. Mapping the bacterial metabolic niche space. Nat Comm 11, 4887 (2020).
[17] McCarty, N. S. & Ledesma-Amaro, R. Synthetic Biology Tools to Engineer Microbial Communities for Biotechnology. Trends Biotechnol. 37, 181–197 (2019).
[18] Smith, T. P. et al. Bacterial responses to complex mixtures of chemical pollutants. Nature MIcrobiol (Accpeted). bioRxiv 2023.02.18.529059 (2023). URL http://biorxiv.org/content/early/2023/02/18/2023.02.18. 529059.abstract.
[19] Smith, T. P., Mombrikotb, S., Ransome, E., Pawar, S. & Bell, T. Latent functional diversity may accelerate microbial community responses to temperature fluctuations. eLife 11, e80867 (2022).

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Project supervisors

Career overview

Samraat Pawar is a Professor of Theoretical Ecology in the Department of Life Sciences at Silwood Park, part of the Faculty of Natural Sciences at Imperial College London. His research focuses on understanding how individual-level metabolism scales up through species interactions to influence community and ecosystem-level dynamics. He is affiliated with several research initiatives, including the Ecosystems and the Environment, the Georgina Mace Centre for the Living Planet, and the Grantham Institute. Prof. Pawar is multilingual, proficient in English, Marathi, Hindi, Spanish (Latin American), and Sanskrit.


Research interests

Professor Pawar''s research focuses on how individual-level metabolism scales up through species interactions to community and ecosystem-level dynamics. His areas of interest include ecology, ecological impacts of climate change, ecosystem function, evolutionary impacts of climate change, microbial ecology, community ecology (excluding invasive species ecology), biological physics, and biological mathematics.

View Professor Samraat Pawar's profile 
Career overview

Cleo Kontoravdi is a Professor of Biological Systems Engineering in the Department of Chemical Engineering at Imperial College London. She has held various academic positions since joining the institution, including Director of Postgraduate Studies from 2021 to the present, Postgraduate Admissions Tutor from 2018 to 2021, and Departmental Athena SWAN Coordinator from 2012 to 2018. Prior to her academic career, she worked as a Research and Development Scientist at Lonza Biologics from 2006 to 2007. Cleo Kontoravdi earned her PhD in Chemical Engineering from Imperial College London in 2007, following her MEng in Chemical Engineering from the same institution in 2002. Her research interests focus on biotechnology, particularly the application of systems engineering principles to bioprocessing, which includes the systematic integration of model-based tools with experimentation on mammalian cell culture systems and vaccine production platforms. She is engaged in topics such as optimisation of culture media and conditions, protein glycosylation, metabolic flux analysis, and multiscale modelling.


Research interests

Professor Kontoravdi''s research focuses on biotechnology, specifically the application of systems engineering principles to bioprocessing. Their work involves the systematic integration of model-based tools, such as sensitivity analysis, design of experiments, and optimisation, with experimentation on mammalian cell culture systems and vaccine production platforms. Key topics of interest include the optimisation of culture media and conditions for productivity, protein glycosylation, metabolic flux analysis, and multiscale modelling.

View Professor Cleo Kontoravdi's profile 
Career overview

Prof. Benoit Chachuat is a Professor of Process Systems Engineering in the Department of Chemical Engineering at Imperial College London, UK. He has held this position since 2020. Prior to this, he was a Reader in Process Systems Engineering at the same department from 2015 to 2020. From 2010 to 2015, he served as a Senior Lecturer in the Department of Chemical Engineering at Imperial College London. His academic career began as an Assistant Professor in the Department of Chemical Engineering at McMaster University in Ontario, Canada, from 2008 to 2010. Before that, he worked as a Research Associate and Lecturer at the Automatic Control Laboratory of the Swiss Federal Institute of Technology in Lausanne (EPFL), Switzerland, from 2005 to 2008. He was a Postdoctoral Associate in the Department of Chemical Engineering at the Massachusetts Institute of Technology (MIT) in the USA from 2003 to 2005, and also held a postdoctoral position with the COMORE Team at INRIA Sophia-Antipolis in France from 2002 to 2003. His early career included a role as a Research and Teaching Assistant at LSGC-CNRS, Lorraine Institute of Technology (INPL) in Nancy, France, from 1998 to 2002. Prof. Chachuat''s research aims to develop safe, economically viable, and environmentally sustainable chemical and biological processes through advanced computational modelling and optimisation methods, collaborating closely with experimentalists. He also focuses on creating software tools to implement these methods for broader dissemination.


Research interests

Professor Chachuat''s research aims to develop safe, economically and environmentally sustainable chemical and biological processes through the synergistic use of advanced computational modelling and optimisation methods alongside process data. His vision of process systems engineering emphasises rigorous computation to predict the performance at scale of both existing and novel technologies, thereby empowering decision-making. He collaborates closely with experimentalists and develops software tools to implement these methods for broader dissemination. His fields of research include Chemical Engineering, Resources Engineering and Extractive Metallurgy, Environmental Engineering, Applied Mathematics, Mechanical Engineering, and Numerical and Computational Mathematics.

View Professor Benoit Chachuat's profile 
Career overview

Rodrigo Ledesma-Amaro obtained his PhD at the University of Salamanca under the supervision of Prof. Jose Luis Revuelta, the head of the metabolic engineering group. The PhD thesis focused on systems metabolic engineering of A. gossypii for the production of vitamins, nucleosides, and lipids, combining modelling, synthetic biology, systems biology, and metabolic engineering techniques, which resulted in numerous research papers and industrial patents currently utilised by BASF. Prior to his PhD, he completed an MSc in Microbial Biotechnology at the Universidad Autonoma de Madrid and two undergraduate degrees in Biotechnology and Chemical Engineering at the University of Salamanca. During his doctoral studies, he was a visiting researcher at Prof. Jens Nielsen''s group at Chalmers University of Technology in Sweden, at Prof. Jean-Marc Nicaud at INRA in France, and at Prof. Kamisaka''s group at AIST in Japan. After completing his PhD, he moved to France under an Agreenskills Marie Curie Fellowship and conducted his postdoctoral research in the group of Jean-Marc Nicaud, primarily focusing on the oleaginous yeast Yarrowia lipolytica. His postdoctoral work involved engineering this organism to produce various compounds, including lipids and carotenoids, utilise low-cost carbon sources such as lignocellulosic materials or starch, and facilitate product recovery through lipid secretion. During this period, he also taught synthetic biology-related subjects at SUP biotech. Rodrigo Ledesma-Amaro has experience in organising international conferences, teaching courses, editorial activities for several publishing groups, and supervising and evaluating students, projects, and researchers. He maintains worldwide collaborations in both academia and industry. Currently, he leads a research group at the interface of synthetic biology and metabolic engineering within the Department of Bioengineering and the Centre for Synthetic Biology and Innovation at Imperial College London.


Research interests

Professor Rodrigo Ledesma Amaro''s research focuses on the intersection of synthetic biology and metabolic engineering. His group is dedicated to developing and utilising new synthetic biology tools for the precise manipulation of microbial cells in a reliable and standardised manner, particularly through techniques that fine-tune metabolic pathways. In the realm of metabolic engineering, the group is interested in manipulating and optimising microbial metabolic pathways, which are crucial for biotechnology and a bio-based economy. They aim to ''hack'' metabolism using synthetic biology tools to create new properties and enhance behaviours in microbial cells. Their engineering strategies target the production of high-value products and the optimisation of bioprocesses. The lab also explores microbial biotechnology and the role of microbial communities in industrial bioprocesses and biomedicine, focusing on a variety of organisms, including yeast (S. cerevisiae and Y. lipolytica), fungi (A. gossypii), and bacteria (E. coli and Acetobacter), as well as complex microbial consortia such as human and industrial microbiota. Applications of their research extend to industrial biotechnology and biomedicine, with interests in producing high-value chemicals and fuels (e.g., biodiesel, lipid-derived compounds, food additives), biomaterials for biomedicine and environmental applications (e.g., bacterial cellulose), and understanding microbiomes and dysbiosis related to diseases, including skin microbiome and wound healing.

View Professor Rodrigo Ledesma Amaro's profile 

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