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!
Last week Bamu successfully defended her PhD dissertation from the questions of her
two examiners: Katharina Schaufler
and Marius Vital.
Congratulations to her for pulling this off as the first hybrid dry- and wet- lab PhD student to graduate from our lab!
