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Biophysicist in Profile

Andrea Gohlke

Andrea Gohlke

July/August 2020 // 5086

Andrea Gohlke is a senior biophysicist in early stage oncology drug discovery at AstraZeneca in Cambridge, United Kingdom. She grew up in a small town called Uelzen, in northern Germany between Hamburg and Hannover. Her father was a mechanics teacher and her mother a shop assistant at a butcher shop. “My path to university was new to them, they would have rather liked me to earn an income directly after school,” she says, “but then they recognized that science was my passion and were very supportive. They are visiting me regularly abroad which is great.”

Gohlke’s favorite subjects in school were math and chemistry. “I liked working with numbers and learning things that were logically connected,” she explains. She graduated secondary school in 2001 and immediately began her under­graduate studies in Molecular Biotechnology and Molecular Life Science at the University of Luebeck, Germany. Her course of study was very interdisciplinary, exposing her to different fields including math, chemistry, biology, physics, informatics, and medicine. She obtained her bachelor of science degree in 2004, followed by a master of science in molecular life science in 2006 at the same university. “During my bachelor’s thesis – titled ‘Calculational Gene Localiza­tion of Dyslexia’ at the Institute of Medical Biometry and Statistics, I focused on biometry and statistics, which I very much enjoyed. But I was missing the lab aspect, so during my master’s thesis, I started to explore the different areas of structural biology and ended up studying galactosyltransfer­ase-ligand interactions using NMR. It was then that I became fascinated with the study of molecular interactions and how to investigate them using physics,” she shares.

She further focused in on biophysics during her PhD studies in the group of Roland Winter at the Technische Universität Dortmund, Germany, in collaboration with the Max Planck Institute for Molecular Physiology. She explored a variety of methods there, including fluorescence microscopy and spectroscopy, infrared reflection absorption spectroscopy, and surface plasmon resonance spectroscopy to study model membrane interactions of Ras and Amylin. This also got her interested in the assembly of model lipid membranes. “The application of different biophysical methods showed me how important it is to validate results but also that it is crucial to know the limitations of each method.” During this time she also had the opportunity to build up a cell lab from scratch, “to build up experiments studying the interaction of amyloids with cell membranes,” she says. Gohlke joined the Interna­tional Max Planck Research Schools program, where she had her first experience planning a conference.

One of Gohlke’s colleagues in Winter’s lab was Claus Czeslik. “We worked together on establishing new techniques in the lab (FCS, confocal microscopy, and IRRAS),” he says. “We also did some teaching activities together — supervising exams, practical trainings, and oral exams of students. Unfortunate­ly we are currently not working together, however we meet once in a while at the Biophysical Society Annual Meeting. Andrea is a very dedicated scientist, simultaneously she has a pronounced sense of humor, which makes working with her very enjoyable and fun.”

In 2010 she started as a postdoc in the lab of Nobel laureate James Rothman at Yale University in the United States. “He received his Nobel prize while I was working for him, thus it was an exciting time,” Gohlke shares. There, she studied SNARE-mediated membrane fusion using biophysics. “My goal was to recreate the process in a model membrane system and study it with TIRF and confocal microscopy on a single vesicle level,” she says. “I developed a new protocol which integrates the t-SNAREs into freestanding bilayer and then studied liposomes containing v-SNAREs fusing to them.”

After two and a half years, she began to find it difficult to be so far from her family. “Fortunately, my collaborator Frederic Pincet at the Ecole Normale Superieure in Paris, France, of­fered me the opportunity to continue my work in his lab while still being supported by James Rothman,” she explains. “Over­all, it was a great experience. I had the chance to directly learn from Jim, who was very supportive and always seemed open to new ideas. He is certainly a person to look up to.”

Her colleague in Pincet’s group, Yong Jian Wang, did not work with her on the same project, but both worked with SNARE proteins. “Andrea Gohlke has many excellent qualities,” he says. “The most memorable one is that she is willing to help others by providing her constructive ideas.”

Following her first postdoc, she thought about how she wanted her career in biophysics to proceed. She was enjoying her academic life, full of new ideas and working on her own project. On the other hand, she longed for some job security and missed teamwork. She applied for a variety of biophyisi­cist positions and in the end was faced with a choice be­tween a postdoc at Imperial College, London, or a long-term contract working in drug discovery at the Beatson Institute for Cancer Research in Scotland, UK. “I was not very familiar with the processes in drug discovery at the time. But as the profile fit right into my interests of studying protein-ligand interaction using biophysics (NMR, ITC, SPR), I decided to go for the position at Beatson as a senior biophysicist,” she says. “I discovered that biophysics is essential in early stage drug discovery and that its correct application is what makes or breaks projects. I also started a new workshop called ‘Know Your Method’ that was held at the Beatson Institute to talk about the right application of certain methods available in the Institute.”

Gohlke now works as a senior biophysicist in early stage oncology drug discovery at AstraZeneca in Cambridge, United Kingdom. As is common within industry research, her projects are confidential, but range over a variety of oncology target classes. “In general, I am using quantitative biophysics (SPR, ITC, etc.) to study drug targets in oncology and their interac­tion with small molecules. This encompasses everything from exploring new drug targets and their mode of action, screen­ing for new initial small molecules, to working on lead series of drug molecules which then have the potential to be tested in the clinics. As I am working on several projects and target classes, each target exhibits its own challenges,” she shares. “I work in a very interdisciplinary environment, in direct con­tact with chemists, biochemists, and cell biologists. We are steadily consulting on how to proceed best with the projects, each of us bringing a different specialist point of view to the table which makes it very creative work. I am also getting more experience in project management and am supervis­ing students here at AstraZeneca which still lets me have a glimpse of the academic world.” In addition, she has recently been volunteering for three months at a COVID-19 screening facility as a data team lead helping to establish the facility and evaluating screening results. “ It has been an invaluable experience being on the forefront making a direct impact in patients’ lives,” she shares.

When asked about some of the challenges she faced in her field, she shares, “Biophysics in drug discovery is sometimes seen as a straightforward approach making it look simple. But as with any method, it is important to familiarize yourself with the principles and limitations of each method thoroughly, as these are sometimes not accounted for when interpreting results. Through establishing a new workshop called ‘Biophysics in Drug Discovery – Not Just a Black Box’ I am trying to raise awareness and get users from industry and academics talking about the technical implications when us­ing biophysical methods. Unfortunately, I had to cancel it due to the COVID-19 lockdown but hope to proceed with it again soon.”

When she is not working, Gohlke enjoys traveling, exploring different cultures, enjoying good food with friends, and going swimming or taking a nice walk in the park with her husband. “I also very much enjoy music. I used to sing in a choir and play instruments, which I want to pick up again,” she shares.

Going forward in her career, Gohlke hopes to use biophysics to advance drug discovery, and to contribute to developing novel methods exhibiting higher sensitivity, with the ability to measure in more physiological environments.

“My advice to biophysicists just starting out in their careers would be that you should always ask for the things you want to achieve,” she says. “Do not wait for someone else to make these decisions for you. In addition, my advice would be to be proactive and honest, standing by your integrity and being respectful to others is essential for great science as much as it is in daily life.”