Developing and validating a computational model of the gut microbiota–mucosa interactions to replace and reduce animal experiments

University of Birmingham School of Biosciences

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Dr J U Kreft Dr T Iqbal No more applications being accepted

Birmingham United Kingdom

About the Project

An explosive growth of research on the gut microbiota, often using rodent models, has amply demonstrated the huge importance of the previously neglected microorganisms for our health. However, the complexity of the system poses a formidable challenge. Our central hypothesis is that mathematical modelling is required to understand and predict such a complex system. Our long-term goal is to replace & reduce animal experiments and improve our understanding by developing and utilizing a general mathematical modelling platform. The specific aim of the studentship is to develop a mathematical model of the gut mucosa as part of our eGUT (electronic gut) software and to validate the model with an in vitro microfluidic and an insect model as well as training the student in a range of alternatives to rodent models. This is timely as research in this area using animal experiments is growing exponentially. By improving the science, we can best realize the potential of eGUT to ultimately replace & reduce ~75,000 animals per year globally.

The project is supervised by Dr Jan-Ulrich Kreft, a computational biologist in the Centre for Computational Biology (CCB), and co-supervised by Prof Tariq Iqbal, a gastroenterologist at the University Hospital Birmingham.

We are looking for enthusiastic candidates who have a strong background in mathematical modelling and computer programming. Ideally, candidates should also have experience with laboratory experiments and knowledge of microbiology and human physiology.
The experiments to validate the model will be conducted at the University of Luxembourg in Prof Wilmes group (in vitro microfluidic model) and at the University of Valencia in Prof Moyes group (insect model). The candidate should therefore be happy to live in Luxembourg and Spain for about 6 months each.

For more information, visit the project description on the NC3Rs website and the description on the Kreft lab pages, where you can also find the grant proposal case for support, which has all the details.

This studentship is funded by the NC3Rs for 3 years. There is no first Masters like year as with other RCUK funded studentships, so you will be starting your PhD project straight away.

Like other Biosciences PhD students, you will need to undertake a limited amount of training throughout your PhD. In addition, you will take part in the NC3Rs summer school and other training events.

You will need to complete the standard University of Birmingham online application form (Biosciences PhD). In the funding section of the form, state that you wish to be considered for the NC3Rs studentship.

Links:

www.egut.org.uk

http://www.nc3rs.org.uk/

https://nc3rs.org.uk/developing-and-validating-computational-model-gut-microbiota-mucosa-interactions-replace-and-reduce

http://www.biosciences-labs.bham.ac.uk/kreftlab/job_adverts/Kreft_NC3Rs_studentship_Case_for_support.pdf

https://scholar.google.co.uk/citations?user=hLRsYpsAAAAJ&hl=en&oi=ao

Funding Notes

The studentship will pay the full tuition fees for UK/EU students and a stipend in line with other RCUK studentships (currently at £14,553) and a generous Research Training Support Grant of £30k.

Unfortunately, RCUK eligibility criteria mean that EU students, unless they have been resident in the UK for more than 3 years, can only receive the tuition fees.

Start date: 1 Oct 2018 or earlier!

Please email j.kreft at bham.ac.uk if you have any questions.

References

Clegg RJ, Kreft JU (2017). Reducing discrepancies between 3D and 2D simulations due to cell packing density. Journal of Theoretical Biology 423: 26–30

Hellweger FL, Clegg RJ, Clark JR, Plugge CM, Kreft J-U. 2016. Advancing microbial sciences by individual-based modelling. Nature Reviews Microbiology 14: 461–471

Widder S, Allen RJ, Pfeiffer T, Curtis TP, Wiuf C, Sloan WT, Cordero OX, Brown SP, Momeni B, Shou W, Kettle H, Flint HJ, Haas AF, Laroche B, Kreft JU, Rainey PB, Freilich S, Schuster S, Milferstedt K, van der Meer JR, Großkopf T, Huisman J, Free A, Picioreanu C, Quince C, Klapper I, Labarthe S, Smets BF, Wang H, Isaac Newton Institute Fellows, Soyer OS (2016). Challenges in microbial ecology: building predictive understanding of community function and dynamics. ISME Journal 10: 2557–2568

Lardon LA, Merkey BV, Martins S, Dötsch A, Picioreanu C, Kreft JU, Smets BF (2011). iDynoMiCS: next-generation individual-based modelling of biofilms. Environmental Microbiology 13: 2416–2434

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Where will I study?

University of Birmingham

For more than a century, the University of Birmingham has been pursuing and sharing knowledge through outstanding teaching and research. As a founding Russell Group member and the original ‘redbrick’ university, our high-quality teaching will help you take your career to the next level. We are of the country’s most consistently sought-after universities by the UK’s top graduate employers, and have been for the last decade. With a wealth of opportunities to choose from across study and research, Birmingham has one of the most extensive postgraduate course portfolios in the UK. Hosting an international community of more than 8000 staff and 38,000 students, you’ll work alongside world-leading academics in a diverse community.

Career overview

Dr Jan-Ulrich Kreft is an Associate Professor in Computational Biology at the University of Birmingham, having joined the institution in September 2007. He studied Biology at the Universities of Konstanz and Tübingen in Germany from October 1985 to August 1991, where he obtained a Diplom Biologe in 1991. He then completed his PhD in Microbiology at the University of Konstanz in June 1995. Following his doctoral studies, Dr Kreft undertook a postdoctoral position with Professor Bernhard Schink at the University of Konstanz until February 1997. He then held a DFG fellowship with Professor Julian Wimpenny at the University of Cardiff from March 1997 to August 1998, subsequently serving as a Postdoctoral Research Associate (BBSRC) with the same professor until August 2001. Dr Kreft''s career continued at the University of Bonn, where he worked as a Wissenschaftlicher Assistent in the Theoretical Biology group of Professor Wolfgang Alt from September 2001 to August 2007. His research primarily focuses on the dynamics of interaction among microbes, particularly in biofilms, and includes the study of cooperation, competition, and communication within microbial communities. He employs individual-based modelling techniques to simulate these interactions and their emergent behaviours. Dr Kreft has collaborated with various institutions, including TU Delft and the Danish Technical University, on projects related to microbial interactions and biofilm structures.

Research interests

Dr Jan-Ulrich Kreft''s research focuses on the dynamics of interaction between individual organisms and how these interactions lead to emergent behaviour at higher levels of organisation, particularly in microbial communities. His specific areas of interest include the cooperation and communication of microbes in biofilms, metabolic division of labour, and individual-based modelling within systems biology. Current research projects include the evolution of cooperation in biofilms, where he studies the economic use of resources and the spatial structure''s impact on bacterial competition; the effects of twitching motility on biofilm structure in *Pseudomonas aeruginosa*; and the mechanisms of horizontal gene transfer in biofilms using spatially explicit individual-based models. Dr Kreft is also investigating the concept of one-step nitrification and the evolutionary implications of cell-cell communication in clustered microbial environments. His work employs individual-based models, such as iDynoMiCS, to simulate and understand microbial interactions and processes.

Microbiology Mathematical Modelling Biofilms Cooperation Communication Metabolic Division of Labour Individual-based Modelling Systems Biology Spatially Structured Systems Horizontal Gene Transfer Nitrification Cell-Cell Communication Quorum Sensing Microbial Ecology Agent-based Modelling Environmental Microbiology

View Dr. Jan-Ulrich Kreft's profile