How chemistry opened the door to a molecular level for Sebastian Schmitt

An everyday lab scene (well, probably as your non-science peers might imagine it)

Not many biologists will keep their first semester practical course in chemistry in especially good memory. Slowly titrating 0.1 M HCl against NaOH while observing the pH is usually a little less thrilling than cooking some methamphetamine with Walter White in the desert of New Mexico (sorry here to all non-Breaking Bad viewers). Nonetheless, chemistry can prove extremely useful when working on a biological question. Here, Sebastian Schmitt, who is a postdoc at the Geyer lab, tells us how his studies in biology as well as chemistry prepared him for his current research. Let’s zoom in!

 

“Science means… a lot to me”

On the first glance, the topics Sebastian has been working on appear quite diverse but typical for a life scientist: lipids in myelin, actin and the mouse brain proteome. Sebastian points out that everything was well connected: “We did the brain proteomics to identify candidates which are important in the differentiation of oligodendrocytes and myelination and from that we also found cytoskeleton regulators, which, in turn, brought us to actin.”

But, let’s pause here for a second. Sebastian is a chemist. How come he ended up preparing actin from rabbit muscles to answer biological questions? To understand this, we need to know a little bit about Sebastian’s career and background. He originally enrolled in a Diploma degree programme in chemistry as well as a teacher training in chemistry and biology. During his studies, he got more and more interested in medicinal chemistry and biochemistry. That was when he realised that those subjects including cell biology were his real passion. Even though Sebastian liked doing “paper chemistry” as he calls planning of complex organic syntheses, he did not see the point in preparing compounds which were only stable under inert gas atmosphere lacking direct application in the “real world”. In order to get deeper into biology, he skipped the teacher training and enrolled into a Diploma programme in biology instead.

 

“I am a genius at… [pause] procrastination” – “I really suck at… [instantaneously] mathematics!”

Now on the biological track, there was one issue left: Although Sebastian had finished his Diploma degree in biology, he also had to finish chemistry because he got BAföG support (German Federal Law on support in Education) for his chemistry studies. This made him graduate both Diploma degree programmes and finally a proper biologist as well as chemist. Fun fact: “I performed my biology Diploma thesis working on heat shock proteins in a model system for oligodendrocytes. Afterwards, I wanted to pursue my chemistry Diploma thesis in a company working on nanoparticles, but when I saw an offer for a Diploma thesis in Ursula Jakob’s lab at the University of Michigan, I just applied. Within a day, I got an answer, and three months later, I found myself on a plane to the US. Here, I could work on molecular chaperones form a more biochemical point of view, which was the perfect complement to my previous work.”

During his PhD with Prof Mikael Simons at the Max Planck Institute for Experimental Medicine Sebastian was sure he could combine his experience in cell biology and biochemistry. However, you should always expect the unexpected when performing a PhD, and things turned out a bit differently: Sebastian continued working on oligodendrocyte differentiation but applying proteomics and mouse genetics approaches which were centred more on an organismal level, driving him even more into the biological direction.

In retrospect, Sebastian adds, also a more specialised course of studies, like biochemistry would have given him similar knowledge and abilities. However, sometimes you have to take a back road, including a little detour to reach your destination. It is not much of a surprise that, while working on the actin cytoskeleton, you don’t need most of what you learn when studying chemistry. But certain knowledge of chemistry can be helpful to estimate if the compound you want to add to your cell cultures is susceptible to degradation, to know which chemicals you can combine in a buffer without precipitation, or to understand why you cannot make a TRIS buffer RNase free using DEPC. Since chemical tools are quite common in biological labs, an education in chemistry also helps to understand how the components of your Co-IP kit crosslink your antibody to the beads or what chemistry is used when you label your recombinant protein or antibody with a fluorescent dye.

In chemistry, you heavily rely on analytical methods, most of which have been refined to analyse biomolecules. Coupling chromatography with mass spectrometry, for example, is often used in analytical chemistry, but is also the basis for modern lipidomics and proteomics. Therefore, Sebastian’s chemical education helps him to better understand what happens with his samples during proteomic analyses.

“Lastly,” Sebastian points out, “a more indirect benefit from a chemical education is that you see things from a rather molecular point of view. Biology on the other hand enables me to zoom out and look at problems from a completely different angle.”

 

“The ImmunoSensation Cluster… provides a great platform for people to get in contact with each other and do things together”

What now and next? “I am currently focussing on understanding how certain regulators of the actin cytoskeleton work and how they affect the morphology and function of cells. We are trying to do this on different levels ranging from molecules to cells and, eventually, even the whole organism.” However, right now Sebastian’s main daily work deals with the molecular level, which means expressing and purifying different regulator proteins and testing how they affect actin polymerisation in vitro. Understanding these regulators also possesses immunological relevance since cytoskeletal rearrangements play decisive roles in cell motility. Indeed, an immunological disorder called Wiskott-Aldrich syndrome was one of the first diseases that was found to be caused by mutations in the gene of an actin regulator.

So, next time you are sitting in front of your favourite FACS machine you might be wondering why your antibody is actually glowing at 519 nm… The chemist will know 😉

 

(featured image: colourbox.com)


Author: Christian Sieg

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