12 December 2017

Interview with Markus Weingarth

Fighting bad bugs with a magnet

Markus Weingarth

Every week day, I get to work with a machine that looks like a large modified version of the Star Wars droid R2-D2. But this is where the resemblance ends. Our machine is a very large magnet that we exploit for a kind of super-microscopy technique called Nuclear Magnetic Resonance (NMR). The NMR magnet operates at ultralow temperatures, -269°C, less than 4 degrees above absolute 0 temperature (-273.15°C). This is achieved by surrounding the magnet in liquid helium, which is in turn enveloped by a jacket of liquid nitrogen. The power of NMR is that we can see molecules at the atomic level. This creative technique can measure the building blocks of everything, from the dirt on your shoe to the cobweb in the corner to a tear drop.

Antibiotic resistance is a global health concern

In the context of human health, we can study the structures and interactions of biomolecules that regulate many of the biological processes in a cell. In particular, my group is interested in antibiotics, which is a research area of high societal importance due to the alarming rise of antimicrobial resistance. 

Resistance to antibiotics is increasing world-wide and threatens effective prevention and treatment of many infections, surgical procedures and cancer treatments. This results in rising health care costs due to prolonged illness and more intensive care.

Therefore, we urgently need novel and better antibiotics. Antibiotics prevent bacterial cells from growing and replicating. For example, antibiotics can occupy receptors on the bacterial cell membrane and prevent binding of certain substances needed for replication and survival, or they can disrupt the structure of the bacterial cell membrane causing improper functioning.

We’re using and developing methods to look, at the atomic-level, at the interaction between the antibiotic and an actual cell membra
NMR Spectroscopy, Faculty of Science

New NMR methods may help overthrow bacterial resistance

My group is using NMR spectroscopy to illuminate the molecular structure of antibiotics and explores how they interact with the bacterial cell membrane. Interestingly, the composition of cell membrane receptors can vary between individual bacteria, and we’re studying how this may contribute to resistance. This may help us find better drug targets or improve existing ones.

What’s really exciting is that we’re using and developing methods to look, at the atomic-level, at the interaction between the antibiotic and an actual cell membrane (as opposed to traditional methods of studying antibiotics dissolved in water), something that was unimaginable five years ago and is still quite unique in the field.

NMR is a powerful tool to measure atomic interactions, however won’t answer all of our questions. Therefore, we’ve integrated computational aspects into our research and can generate simulations for these types of interactions. For example, if there’s a mutation in a protein in the bacterial cell membrane, we can simulate the interaction between the antibiotic and the mutated membrane protein and predict whether the mutation causes improper binding and function of the antibiotic. Ultimately, this may allow us to design more specific therapies in order to kill these bad bugs.