© Christian Hofer
November 2019 − Research Careers
Vienna-based molecular biologist Georg Winter intends to eliminate cancer-causing proteins on the spot. To this end, he pursues a novel approach to “waste disposal” in the human body.
In our bodies, waste disposal occurs strictly according to plan: the garbage is collected on a regular basis; it is sorted, recycled or incinerated. What happens, though, if waste collection goes on strike? The entire process will grind to a halt: mountains of waste will pile up outside our door; they will attract rats and mice – reminiscent of those conditions that in the late Middle Ages led to outbreaks of the plague.
Just like a metropolis, every single cell in the human body possesses a perfectly orchestrated system for waste removal. It transports defective proteins that come off the conveyor belts of the cellular protein factories to the cell’s proteasome, where they are shredded.
This process is of crucial importance to the organism, as these faulty proteins contribute to the development of cancer. However: each system has its weaknesses, and some of the disease-relevant proteins will slip through the cracks of the self-cleaning program because they are not discovered and they are therefore not identified as harmful. This is where Dr. Georg Winter enters the stage of the cellular waste management operation and engages in systematic clean-up.
Action on the spot
How? By blazing new trails as a researcher. “The basic problem is that by using conventional therapeutics, we are able to block only about twenty percent of all disease-relevant proteins”, explains the molecular biologist who, for the past two and a half years, has been spearheading a research team of six at the Research Center for Molecular Medicine (CeMM) of the Austrian Academy of Sciences (ÖAW) in Vienna. According to Winter, the problem is rooted in the way that we look at medication: “Medication is defined as a chemical substance that binds to a biochemical activity within a protein by docking directly into a ‘pocket’”. Many disease-relevant proteins, however, do not possess such a pocket. The Austrian therefore pursues a different strategy. He wants to not only block the faulty proteins, but he wants to make short work of them right then and there. To this end, he is attempting to reprogram the body’s own protein degradation machinery using novel agents.
The main actors on Winter’s disposal team are enzymes called ubiquitin ligases. “We have developed molecules which ensure that disease-causing proteins dock directly onto those ligases. In this way, they are labeled and eliminated within minutes.” Bingo! Georg Winter has achieved his goal – this discovery has afforded him his own personal moon landing. “This is the exact feeling I have when I discover something that nobody else in the world has been able to explain!” He laughs, and he adds: “This is incredibly motivating.”
The tireless scientist
Georg Winter is a doer, an energy person, a solution-nerd. When the unknown calls, he does not hesitate. “I like being hands-on – just trying things out and not spending too much time fretting in advance why it may not work”, says the 33-year-old who does not lose sleep if an experiment fails. “I’ll just try again – and again – until it works.”
Research electrifies the microbiologist, and he knows exactly how it works: “You need dialogue, not isolation.” The team player has his best ideas during discussions with his students and colleagues. “I love collaborating, brainstorming and developing new concepts together with others.” To Winter, thinking outside the box is not a voluntary exercise; it is a duty: “Research needs lateral thinkers and boundary pushers.”
Following his bachelor studies of molecular biotechnology at the FH Campus Vienna, he earned his doctorate from the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences. His subsequent move to the renowned Harvard University® happened by “planned coincidence”, as Winter describes it. By chance, he met his future mentor, head of a laboratory at the Dana Farber Cancer Institute at Harvard Medical School, at a conference in Boston. And – equally by chance – Georg Winter started his three-year postdoc in Boston not long after. He was at the right place at exactly the right time.
With his research group, situated at the intersection between gene regulation, cancer development and chemical biology, he developed a new type of therapeutic agent that breaks down cancer-relevant proteins. For his pioneering work which, back in Austria at the CeMM, he is in the process of adapting to general application, Georg Winter has already been recognized and awarded a number of prizes – most recently the Eppendorf Award for Young European Investigators 2019.
The starting signal
The basis of the active therapeutic agent is a substance that was at the root of the largest scandal in the history of medicine: thalidomide. The tranquilizer was prescribed to pregnant women between 1957 and 1961 to treat morning sickness – with tragic consequences: the babies were born with severe malformations. A dangerous drug as a new hope for modern cancer research? “Thalidomide is one of the saddest chapters in pharmaceutical research” regrets Georg Winter. “However, in the 1990s it was discovered that thalidomide derivatives were capable of eliminating cancer cells.” The mechanism of action was not discovered until 20 years later: inside the cell, the substances bind to ubiquitin ligase which regulates protein degradation. “That was the starting signal for our research!”
Georg Winter has a vision: to develop a drug that “makes a difference in patients’ lives” – that paves the way to good health. For the scientist, this would be his own personal jackpot. And those who know Georg Winter, his competence, his team spirit, his ambition, his curiosity and his patience, will have no doubt that he will win.
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„nature“ – podcast with Georg Winter!:
© Christian Hofer
© Christian Hofer
© Christian Hofer