The final piece of the puzzle

Professor Michael Mayer joined the Adolphe Merkle Institute at the end of 2015 as the chair of biophysics. His arrival from the University of Michigan was significant as he was the last full professor to be hired by the University of Fribourg and the institute, finalizing the plan to create an interdisciplinary team focusing on polymer science, bionanomaterials, physics and biophysics.

We find out here what brought Mayer to Fribourg and what his research plans are.   

 

 

First perhaps, just what is biophysics in a nutshell?

Michael Mayer: Biophysics looks quantitatively at biological and biochemical processes. That includes cell biology and physiology. The goal is to measure, understand, and predict reactions that are relevant for living systems. A good example is the structure of proteins. You determine the exact placement of each atom in the molecule and that helps understand how it behaves, what its function might be, or how it might interact with a pharmaceutical. The double helix structure of DNA is another example: it is quintessential biophysics in how it explains the ability of living cells to copy their genetic material and to pass it on to their offspring.

My first contact with biophysics came through undergraduate research on enzymes and electrodes. My initial interest was in the marriage between biochemistry and the physical measurement. Then I became fascinated with how single molecules function. It is amazing to literally watch a single protein in action and see how it can act as a nanoscopic machine, valve, or converter. The goal in biophysics is to understand processes in biology to the point where you can make predictions by developing models, like how a cell communicates, responds to stimuli, or deals with toxins.

What is the main thrust of the research you wish to pursue at AMI?

We apply biophysics with the goal to improve human health by examining detailed aspects of physiology and pathophysiology.  We hope that the resulting insight will reveal strategies toward early-stage diagnostics as well as fresh approaches to therapeutic intervention.

What are the specific projects you believe will have the biggest impact in terms of research and why?

I see three main thrusts. One involves Alzheimer’s disease. We use nanopores to examine Alzheimer amyloid clumps, proteins that are believed to be involved in disease development. We examine those clumps to understand which ones are the most harmful. They come in different sizes and shapes, so their impact is variable. Single molecule biophysics allows us to use tailor-made approaches to examine these proteins and their neurotoxic activity.  Identifying and quantifying the most toxic amyloid assemblies may help to deactivate such toxins.

Another thrust is resistance to chemotherapy in cancer treatment. One resistance mechanism is related to so-called pump proteins found in cells all over the body. Usually these proteins remove toxic chemicals by pumping them out of the cells, which is why they are sometimes called the vacuum cleaners of the cell.  During chemotherapy, cancer cells, which happen to be equipped with many of these vacuum cleaner proteins, have an advantage because they keep the concentration of the chemotherapeutic medicine in the cancer cells low and allow them to multiply despite aggressive treatment.  After some time, the remaining cancer cells are packed full with these vacuum cleaner proteins and resistant to the treatment.  The cancer then continues to grow and even switching therapy does not solve the problem because these vacuum cleaners kick out other medicines as well.

We are interested in these pump proteins. We want to know how they work and how, for instance, the electrical potential across the membrane of the cancer cell controls their function.  We hope this insight may help to fight resistance by turning the activity of these pumps against the cancer cells. 

Finally, we want to detect, characterize, and count proteins one-by-one in biofluids with the aim of discovering biomarkers for disease but also with the aim of improving traditional protein analysis. Every “bio” lab around the world runs traditional gel electrophoresis for protein detection. But this is a somewhat antiquated way of doing things. Using nanopores, tiny holes in a very thin insulating film, we should be able do the same, but much faster, with smaller samples and with higher quality data. Ultimately, we envision a desktop detection system with standardized nanopore chips that count and identify molecules one-by-one in a matter of seconds.

You were working at a major US university (Michigan) as a professor. What made you consider a job in Switzerland?

I was interested in an exciting opportunity to come back to Europe that could compare favorably with top-notch research institutions in the US. Once I visited, I liked the atmosphere, colleagues and infrastructure. I saw an excellent fit with my research, in particular the bio-inspired aspect. Having worked previously in Switzerland, I knew its potential for high-level research – and, it didn’t hurt that knew the beauty of the country.

What specifically attracted you to the AMI?

The NCCR Bio-Inspired Materials played a big role. The leadership and caliber of the colleagues at the institute was also important, along with the whole atmosphere and the support that is available.  For me, research support at the AMI is on the level of the Swiss Federal Institutes of Technology and may even exceed it in some aspects. It was clear as well that there is an excellent infrastructure and funding environment available. The AMI has a well-selected and unique position among the country’s main research hubs. The research in my lab is also very interdisciplinary, so there is an excellent fit for my group to collaborate with the other groups at AMI.

Biophysics is in a sense a hybrid. How do you see that fitting with the research environment at AMI?

If you look at the ongoing projects here at the AMI, many of them take inspiration from biology or examine the interaction of nanomaterials with biology.  Our research can strengthen these projects by developing assays and models that allow us to understand, predict, and enhance their function and performance.

Adolphe Merkle Institute - Chemin des Verdiers 4 - CH-1700 Fribourg - Phone +41 26 300 9254