Andrew Farr
For further information on the projects please refer to
https://scholar.google.com/citations?user=QieKLQ8AAAAJ&hl=en and https://www.evolbio.mpg.de/3792483/Research-Group-for-Microbial-Genetics
or contact Andrew Farr <afarr@evolbio.mpg.de> after having read the recommended literature.
Please submit your application documents via our online portal.
1. Promoter activity as a source of mutagenesis in Bacteria
The evolution of life requires mutation. Mutations are typically rare and in random positions, yet genomes may feature “mutational hotspots” – specific regions with a high mutation rate. Genetic structures such as tandem repeats and palindromes may cause such hotspots, which in the right ecological conditions produce high levels of variation and cause adaptive outcomes.
Recent studies from our department have led to the surprising identification of a hotspot within the promoter of a gene. The promoter for ‘rpoS’ in the species Pseudomonas fluorescens SBW25 features a specific point mutation rate ~5000x higher than expected. Left unknown is the mechanism which results in this high rate of mutagenesis. Might this hotspot be present in many other promoters? Might such hotspots be present in other microbial species? This project will answer these questions and is ready for advancement by a capable and energetic candidate.
The candidate will join a new group within the existing department of Microbial Population Biology. Successful candidates will be creative and imaginative, have a passion for biology and will aim for an academic career. Previous knowledge and experimental experience of genetics, evolutionary biology or microbial ecology will be advantageous. Candidates will be trained to use standard microbial genetic techniques (genetic manipulation, genomics, flow cytometry, Q-PCR, microscopy etc.) and other techniques such as bioinformatics will be employed as required.
General background:
Horton, J. S., & Taylor, T. B. (2023). Mutation bias and adaptation in bacteria. Microbiology (Reading), 169(11). doi:10.1099/mic.0.001404
Specific background:
Farr AD, Vasileiou C, Lind PA, Rainey PB. 2024 An extreme mutational hotspot in nlpD depends on transcriptional induction of rpoS. bioRxiv. (doi:10.1101/2024.07.11.603030)
2. Experimental measurement of factors that limit “Pan-resistance”
The root cause of the antibiotic resistance crisis is perceived to be anthropogenic: from the insufficient production of new antibiotics, to the inappropriate use of antibiotics in agriculture or the clinic. Yet there is an inevitability to the evolution of antibiotic resistance; antibiotic resistance genes (ARGs) are pervasive across microbial ecosystems, and this ‘resistome’ provides pathogenic bacteria with a tool-kit for antibiotic deactivation.
In this project, we will gain experimental insight into the eco-evolutionary forces that alter the benefits of ARGs as they cross the species barrier. We will establish model systems which simulate the transfer of ARGs from reservoir species to recipient target species (using non-pathogenic model systems), and systematically test genetic and ecological factors that influence the benefit of ARGs once transferred. One such factor we will investigate is cross-protection; the degradation of antibiotics by resistant strains resulting in the survival of sensitive strains.
The candidate will be joining a new group within the existing department of Microbial Population Biology. Candidates will be trained in genetic manipulation and appropriate experimental measurements (flow cytometry, microscopy, amplicon or genetic sequencing etc). We are looking for a career-minded young scientist, motivated to understand fundamental forces in microbial evolution and ecology. Previous experience with microbial genetics and experimental microbiology will be helpful, but candidates with modelling or bioinformatics skillsets previously applied to the study of antibiotic resistance are also encouraged to apply.
General background:
Waglechner, N., Wright, G.D. Antibiotic resistance: it’s bad, but why isn’t it worse?. BMC Biol 15, 84 (2017). https://doi.org/10.1186/s12915-017-0423-1
A related project which modelled cross-protection dynamics:
Geyrhofer L, Ruelens P, Farr AD, Pesce D, de Visser JAGM, Brenner N. 2023. Minimal Surviving Inoculum in Collective Antibiotic Resistance. mBio 14:e02456-22.