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PhD/Postdoc Population genetic models for the interplay between CRISPR systems and plasmids in bacteria

Cluster of Excellence CMFI | now

Together with Hildegard Uecker at the MPI in Plön, Junior Research Group Leader Franz Baumdicker looking for a PhD student (d/f/m) interested to study mathematical models for the interplay between plasmids and CRISPR-Cas systems.
The project will be based in Tübingen but includes the possibility of multiple longer research visits at the MPI in Plön.
The PhD project will be co-supervised by the two PIs Hildegard Uecker and Franz Baumdicker.

Announcement for this position:
We are seeking a motivated candidate for joining our Research Group for Mathematical and Computational Population Genetics, at the University of Tübingen in a Ph.D. project on the population genetics of plasmids and CRISPR systems.

The revolutionary CRISPR/Cas technology to edit genomes has its origin in the natural CRISPR-Cas
defense systems of bacteria and archaea. These systems essentially work by cutting foreign
DNA (e.g. phage DNA) at specific spots. Some types of CRISPR are preferentially encoded on
plasmids, which are extra-chromosomal DNA elements. So-called conjugative plasmids can
horizontally transfer between bacterial cells and thus introduce the CRISPR system into other cells.
CRISPR systems have some remarkable properties that make them particularly interesting for both
theoretical as well as applied investigations. To identify specific foreign DNA, the CRISPR system
contains an array of spacers that align with these targets. This array is itself subject to evolutionary
forces including deletion, and selection. Based on their ability to target specific DNA sequences,
CRISPR systems could help to re-sensitize resistant pathogenic strains to antibiotic treatment --
they could be used to eliminate other plasmids that carry antibiotic resistance genes.

The aim of this project is to develop mathematical models for the eco-evolutionary dynamics of
plasmid-encoded CRISPR systems within the framework of theoretical population genetics and to
explore their potential as a therapeutic intervention against antibiotic-resistant bacteria. Possible
questions include: Do plasmids use CRISPR systems to compete with other plasmids? How does
the copy number of resistance plasmids affect the chance of successful elimination through mobile
CRISPR systems? How can we optimize the outcome of a combined antibiotic drug and CRISPR-based
re-sensitizing treatment?

On the mathematical side, the project involves stochastic modeling in combination with
deterministic approaches using branching processes as well as diffusion theory. An optional
computational side of the project can involve simulation-based inference as well as quantitative
analysis of sequenced CRISPR arrays on plasmids. Depending on the interests and profile of the
student, the focus can be more on analytical work or on computer simulations.

Applicants should have a degree preferably in mathematics or physics, or alternatively in computer
science, quantitative biology, or another related field. Good quantitative skills are essential.
Experience in mathematical modeling and knowledge of a programming language is an advantage.

Alternatively, it would also be possible to tackle this project as part of a Postdoc position in our group.

The position, paid according to TV-L 13, is funded by the Cluster of Excellence “Controlling Microbes to Fight Infections” (CMFI) in Tübingen and accordingly does not include teaching duties, but the opportunity to participate in teaching

Papers of interest:
Santer, M. and Uecker, H. (2020). Evolutionary rescue and drug resistance on multicopy plasmids.
Genetics 215(3): 847-868.
Baumdicker, F., Huebner, A.M.I., and Pfaffelhuber, P. (2018). The independent loss model with ordered insertions for the evolution of CRISPR spacers. Theor. Popul. Biol. 119, 72–82.

If you have any questions about the project or the position, please feel free to write to franz.baumdicker@uni-tuebingen.de

Please apply by email to franz.baumdicker@uni-tuebingen.de with a subject line in the following style:
PhD (or PostDoc) Application -- CRISPR Evolution -- Your Name

Please send your application as a single PDF file and include a brief statement of your interests and experience, a CV (including a list of possible publications and contact information for two academic references), and university transcripts.

Your contribution will make a significant difference in our young and agile research groups. Research in the Baumdicker group is primarily focused on mathematical and computational approaches to explain microbial evolution. We are part of two Clusters of Excellence in Tübingen, namely the Clusters "Controlling Microbes to Fight Infections" (CMFI) and "Machine Learning in Science". Our work spans collaborations with biologists to mathematicians. We mainly use population genetics, diffusion theory, stochastic processes, and phylogenetics approaches. In all our projects we aim to obtain not only theoretical results but also applicable computational tools for biological data. Therefore we implement inference, estimation, and analysis tools using phylogenetics, simulations, and machine learning approaches to analyze human and prokaryotic genome data.

For more information about the Uecker Group collaborating on this project, visit http://web.evolbio.mpg.de/stochdyn/.

Besides individual mentoring and guidance for your individual career development, we provide detailed scientific training and open, community-focused science communication. Beyond scientific publications, this will include conference visits, organization and attendance of workshops, and possible research visits to other universities or international summer schools.

If you are not as keen on the evolution of CRISPR as we are, but would still like to join the group, please get in touch with us anyway. We might have further funding resources that might suit you. In this case, the main topic of the PhD project can be developed together in a discussion with the candidate.