Disciplinary Domain of Science and Technology

Researcher profile: Sebastian Deindl

One of the techniques Sebastian Deindl uses in his research is to label purified enzymes with small fluorescent molecules and visualize them using laser light and a self-assembled microscope. Foto: Mark Harris

Protein machines at work, visualized in real time

Individual molecules and proteins that interact with each other and with DNA can now be studied in real time using powerful microscopical techniques such as single-molecule microscopy. This helps researchers better understand various medical conditions. It is not easy, however, and not a skill that can be picked up by just anyone.

Most chemical reactions in our bodies are catalyzed by specialized proteins. How these minuscule but complicated protein machines work at a molecular level can now be studied thanks to powerful microscopical techniques. Even individual molecules can be studied using the microscopical techniques in which Sebastian Deindl has become expert during his time as a postdoc at Harvard University – techniques he now brings to Uppsala Biomedical Centre and Uppsala. The very high spatial and temporal resolutions enable the study of proteins that interact with our genetic material, or are involved in vital cellular transport processes.

“These techniques are extremely powerful, the state of the art in molecular imaging. At Harvard, we studied the specialized protein machines that can modify how genetic material can be packaged as chromatin, with investigations at the molecular level,” says Sebastian Deindl.

He will now be using his knowledge of single-molecule fluorescence imaging techniques to establish how specialized proteins look at a molecular level and how they move, making it possible to link movement to function. It has not been easy, and it took a while to get the knack of it, he says. It is also hard to get sufficiently good data to enable the powerful technique to be used to the full. Designing and setting up the experiments are complicated, and it is vital to get a sufficiently good signal and resolution so you can see what you want to see. But he has learnt from one of the best, Xiaowei Zhuang, a pioneer and internationally recognized researcher in single-molecule biology. This invaluable training has made possible his current work to elucidate the molecular mechanisms by which protein machines work in our cells.

“If we can understand the molecular mechanisms that control the protein machines that act upon our genetic material, we can go on to understand their role in human health and disease. Many of the diseases we humans suffer from are due to one or more of our vital protein machines not working as they should.”

Sebastian is now in the middle of an intensive effort to build up his research team at SciLifeLab, and has high ambitions for what they will achieve. He thinks the Uppsala-Stockholm region is an attractive one, with much to offer in terms of infrastructure and the type of biology that interests him. In the lab next door is Johan Elf, another expert in the field. He sees this as extremely beneficial.

“We want to advance the technology behind single-molecule imaging so that in the future, we will be able to combine more effectively our knowledge of the structure of protein machines with the way they dynamically change and move in order to work. Our desire is to achieve the ultimate quantitative and mechanistic understanding, by visualizing the work of protein machines in something that could be described as molecular films.”

 

Susanna Eriksson

FACTS SEBASTIAN DEINDL

Title: Associate senior lecturer at the Department of Cell and Molecular Biology, Uppsala University

Education: Master of Biochemistry, Eberhard Karls Universität Tübingen, Germany; PhD in Biochemistry, University of California at Berkeley, USA

What about Uppsala? Uppsala is great! Science-wise and as a place to live

Leisure activities: Hiking, windsurfing, surfing, reading, friends, traveling

Reads: Too many scientific papers and not enough books these days

Wanted to be as a child: A scientist (seriously, what did I think?)

Strength: I do not get discouraged easily and typically see challenges rather than obstacles.

Weakness: I can be a bit of a perfectionist!

Dreams about: At least some of our most ambitious scientific projects to come through and work out!