News from the lab

After a rather long hiatus we are hiring again!

We are looking for a candidate to fill a computational PhD student position, with the main task of better understanding which genetic elements (“genes”) make bacterial pathogens such as E. coli, K. pneumoniae, P. aeruginosa, and E. faecium virulent and resistant to antibiotics. We have in fact developed methods (here and here) to sift through large numbers of bacterial genomes for this exact purpose (see here, here, and here), and it will be the job of the candidate to use and improve these methods so that they can be applied to an even larger number of genomes. We are also particularly interested in implementing more machine learning methods and to integrate molecular phenotypes such as gene expression and proteomics.

Our lab is part of the RESIST excellence cluster at Hannover Medical School (MHH), and we are part of a collaborative project with Susanne Häussler and Meike Stiesch to identify genetic determinants of pathogenicity and virulence in life-threatening bacterial infections.

We are looking for a candidate with a strong computational background and relevant technical skills:

• Strong background in computational biology, bioinformatics, computer science, or a related field.
• Experience with programming languages such as Python and workflow management systems such as Snakemake.
• Familiarity with machine learning techniques and libraries (e.g., scikit-learn, TensorFlow, PyTorch).
• Knowledge of bacterial genomics and related bioinformatic tools.
• Experience with high-performance computing (HPC).
• Experience with version control systems (e.g., git) and software development best practices.
• Experience with statistical analysis and data visualization.

We offer a fully-funded PhD position for a little longer than 3 years, to begin in February 2026. The student will be enrolled in the Biomedas graduate program, which offers curriculum specifically designed for computational biology students. The lab is located at Twincore, embedded in a large scientific campus that include Hannover Medical School, and the Center for Individualized Infection Medicine (CiiM); we are also part of the Helmholtz Centre for Infection Research (HZI), which offers lots of opportunities for collaboration.

Hannover is the capital of Lower Saxony, in northern Germany, and is an affordable and vibrant city.

Please apply as soon as possible by sending the following documents to Marco Galardini at marco.galardini@twincore.de:

1. Your CV
2. A short motivation letter
3. The link to a software portfolio (e.g., your GitHub account)
4. Contact details of two references

Yesterday we had the great pleasure to see not only one, but two of our students defending their PhD dissertations! We started off with Judit, who focused on the use of large genome collections to study the transmission of bacterial pathogens in the clinic and on methods to improve current practices for genomic epidemiology. She sustained a rather long Q&A session from her examiners: Conor Meehan and Dirk Schlüter. Then it was time for Hannes to talk about his work on using k-mer based methods to improve the interpretability of bacterial GWAS and aid the design of antimicrobials based on antisense oligonucleotides (i.e. asobiotics), using very large genome collections. He had to contend with a similarly though Q&A session from his examiners: Franziska Faber and Daniel Depledge, who is by now a regular examiner for our PhD students.

After a delicious BBQ organized at our department by them, we headed back to MHH for the graduation ceremony, where we had a pleasant surprise: Judit won the “Infection Biology Prize” for her thesis, which comes with a cool check for 1000 Euros!

Thanks to both for their very hard work and lovely day of celebrations!

People familiar with the field of bacterial genomics have long been aware that microbial genomes are densely packed with genes, and thus are depleted of so-called “junk DNA” (a term that has fallen out of fashion by the way!). As a result, the more abundant protein coding portions of these genomes get the most attention from researchers aiming to find which genetic variants explain phenotypic variation among isolates. Previous work has however already shown that bacterial non-coding regions are both highly diverse and show signals of being evolutionarly constrained. We also knew that these regions influence the expression of genes encoded directly downstream from them. We therefore hypothesized that we could uncover statistical associations between genetic variants in non-coding regions and gene expression variability across isolates.

The results of this work have just been published as a preprint, a work that was led by Bamu during her time as a PhD student in the lab. Bamu was the very first person brave enough to join the lab, and has manged to work both in the dry- and wet-lab, a feat that not many people can achieve!

Bamu indeed found that it was possible to identify at least one genetic variant whose presence was associated with gene expression changes in up to 39% of tested genes in two important bacterial pathogens (E. coli and P. aeruginosa). Using the right way to represent the complex genetic variation (i.e. gene-centric k-mers) allowed Bamu to capture the highest proportion of associations.

Once we found these associations, the next task would be to validate some of them and to understand the actual mechanism operating behind the scene. Here Bamu used a combination of in-silico and in-vitro approaches, which very clearly indicated that no single mechanism would be sufficient to explain the observed associations.

The last part of the study was instead dedicated to the understanding of the role of non-coding genetic variation to antimicrobial resistance. Again, Bamu used her dry- and wet-lab skills to show that indeed there are non-coding variants in both species that are associated with antimicrobial resistance. This leads us to conclude that these often neglected regions of the bacterial genome need to be taken into account if we want to be eventually able to make the most out of bacterial genomes.

We are very happy to report that the third and fourth PhD theses from the lab have been submitted last month!

This time we had a “tale of two theses”; Judit had her thesis 99% ready more than a week before the deadline (!), while Hannes preferred to keep things interesting by having it ready just a day or so before it was due. The steady flow of coffee and tea cups at his desk surely helped!

Regardless, we are all excited about their hard work and are now looking forward to the public defenses in June.

Congratulations to both!

Our paper describing the microGWAS pipeline was published yesterday in the journal Microbial Genomics. We made lots of fixes and additions to the code/documentation since the preprint version, including a hard to reproduce bug that only showed up in a specific HPC 🥵

As you can see from the photo (taken by the RESIST press office) we were quite happy that the publication date coincided with the International Day of Women and Girls in Science!