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!
We are very happy to report that the second PhD thesis from the lab has been submitted last week!
With a whole weekend to spare before the deadline (!), Bamu has submitted her
thesis to the ZIB office. Now we wait for the public defense in January.
Congratulations to Bamu for this hard-earned achievement!
We have just posted a new preprint describing some work we did in the area of
in-vitro laboratory evolution and next generation antibiotics! Here’s a quick explainer
about what we (former postdoc Adam, with help from
Hien, and in collaboration with
Jörg Vogel’s group at the HIRI)
did.
By now, the general public is likely aware of the risks posed by infections from bugs that are
resistant to antibiotics. Whether we could surely argue if the widely circulated estimates
of current and
future deaths caused by antimicrobial resistance are overblown, one thing is
certain: whenever a new antibiotic is introduced, resistance will very quickly follow.
Could there be a way to outpace evolution?
A possible solution to this “arms race” is to develop an antibiotic
that can be quickly and easily updated to target resistant bugs.
An emerging solution is the development of so called antisense oligos (ASOs), which are
a short string of nucleotides (the “building blocks” of DNA) designed to
very specifically block
key genes in the target bacteria.
Given their “lego” like nature, these ASOs are very easy to design, and more importantly
to be updated if the target sequence changes to escape the ASO’s lethal effect.
An easy to understand parallel can be made with covid mRNA vaccines, which are also based
on a (longer) string of nucleotides, and which
have been quickly updated as new variants have emerged.
But, as it is very frequently the case in biology, how organisms will adapt to
a new challenge is very difficult to predict
(“in the most carefully constructed experiment under the most carefully controlled conditions, the organism will do whatever it damn well pleases”).
We therefore set to collect data using a realistic set of antimicrobial ASOs (for which we are using the new proposed term “asobiotics”)
and four nasty bacterial pathogens.
Given that an asobiotic needs a cell delivery component to reach the inside of a bacterial cell to exert its effect,
we hypothesized that we would see two classes of adaptive mutations being induced after treatment: one shutting the cell down
from the entry of the asobiotic, and one changing the target DNA sequence so that even if the asobiotic entered the cell
it would not have been able to bother its growth.
We indeed observed the two classes of mutations appearing (and the second class of mutations had never been reported before),
which confirms that in general bacteria
are very good at escaping whichever treatment we throw at them. But interestingly, which of the two kinds of
mutations would appear was heavily dependent on the nature of the cell delivery mechanism.
Given that cell delivery is harder to update than the “lego” like part, we propose that
particular care should be given to the choice of a delivery mechanism for which resistance
is induced at the lowest possible frequency. By following this simple advice and continuing in
improving this new class of antibiotics we are hoping to eventually be able
to keep up with the evolution of antimicrobial resistance.
Last week we (Hannes, Hien, and Judit) attended the annual meeting of all doctoral students from the
Helmholtz Center for Infection Research (HZI),
which took place at the Helmholtz Institute for RNA-based Infection Research (HIRI)
in WĂĽrzburg.
The event provided an excellent opportunity for us to network and discuss both current and future challenges in infection research.
A highlight of the meeting was the “Night Science Workshop”, led by Itai Yanai (NYU).
The workshop focused on the creative side of scientific discovery, exploring how new hypotheses and questions arise and how creativity drives the scientific progress.
The term “night science” was initially described by François Jacob (a Nobel Prize winning biologist).
In his autobiography he wrote:
Night science wanders blindi. It hesitates, stumbles, recoils, sweats, wakes with a start.
Doubting everything, it is forever trying to find itself, question itself, pull itself back together.
Night science is a sort of workshop of the possible where what will become the building material of
science is worked out.
Following this idea, we were able to practice our creative thinking, improvisation skills and
idea exploration, through different exercises. One example exercise, which was more challenging than expected,
was to explain our project to another person who does not know anything about it, in “day science” speak first,
and then try to translate it into “night science” speak. The “night science”-language is less rigid in
its description of scientific processes, often using metaphors and analogies, making it more accessible
to people without niche scientific knowledge (something similar to what we did in our last lab retreat).
As young researchers, we are mostly taught the language of “day science”, unaware of the
“night science”-aspect of research, which allows us to gather ideas more freely
and provides a safe space to generate hypotheses without the usual restraints of formal scientific correctness.
The meeting also covered the aspects of “day science”, by having the opportunity to present a poster
on our lab’s research and methods. Additionally, Judit could present part of her PhD project,
in particular the “microGWAS pipeline”,
which has been developed together with Bamu, Jenny and Marco, and recently submitted as a preprint.
Overall, it was a great experience, and we definitely recommend the other HZI’s graduate students
attending next year’s assembly, which is likely taking place at Twincore, our own turf!
