Karim Rafie joins University of Groningen as new group leader
Karim Rafie, from the lab of Lars-Anders Carlson, MIMS Investigator, is about to start his independent research group as assistant professor at the University of Groningen in the Netherlands to study how viruses alter mitochondrial function in the cell for the benefit of their own replication.
Articel originally published at MIMS/Umeå University's website at https://www.umu.se/en/news/karim-rafie-joins-university-of-groningen-as-new-group-leader-_11807400/
From chemical biology to structure biology
Karim Rafie comes from a scientific background in chemical biology and was until now a postdoctoral researcher at Umeå University since 2018. He is embarking on a new phase of his scientific career as a junior group leader. During the past five years, Karim has been a part of the research group led by Lars-Anders Carlson, who is an associate professor at the Department of Medical Biochemistry and Biophysics, a Wallenberg Molecular Medicine Fellow, MIMS Investigator and UCMR Principal Investigator, and Karim has had the opportunity of working alongside him. He reflects on his career path and experience in Umeå.
“The chemical biology program I studied in Dortmund, Germany, was essentially developed by a few groups from the local Max Planck Institute together with the Faculty of Chemistry from the university. They wanted to teach students how to apply chemistry to answer biological questions. I knew from high school that I wanted to go into biological sciences but more from the chemistry angle. I only realized after I started my bachelor studies that for me, this was exactly the right balance between the two disciplines”, explains Karim.
Throughout his bachelor's and master's degree in Dortmund, he focused mostly on biophysical methods and structural biology as these were the most interesting topics for Karim. This led him to Dundee, Scottland, to the group of Professor Daan van Aalten (who is also affiliated with Aarhus University, Denmark), first as a master student thanks to the EU-funded student exchange program, Erasmus, then again for his PhD studies. Two main projects were running in Daan’s lab from which one was the post-translational modification protein, O-GlcNac, still not fully understood to this day. O-GlcNAc stands for O-linked GlcNAc or O-linked β-N-acetylglucosamine, and it is a reversible enzymatic post-translational modification that is found on serine and threonine residues of nucleocytoplasmic proteins. It is a simple sugar modification, found in thousands of proteins, regulated by two enzymes; O-GlcNAc transferase and O-GlcNAcase. Interestingly, removing any of these two enzymes during embryogenic development proves to be lethal.
“I joined Daan’s lab because I wanted to learn about protein crystallography and structure biology, and he also worked on drug discovery for fungal pathogens by looking at the biosynthesis of the fungal cell wall. I wanted to work on these, and I was very excited to join the group”, says Karim. “I was naïve, I didn’t have a question in mind, just knew what methods I wanted to use. It was Daan who taught me that it’s not the method, it’s the biological question that matters.”
During his PhD, Karim developed chemical tools to perturb the function of the two enzymes that attach sugar to proteins, by trying to understand how the enzyme binds to its substrates and to use this knowledge to develop bisubstrate inhibitors. In addition, Karim also got a comprehensive understanding of drug design. This was quite serendipitous, as towards the end of his undergraduate studies Karim gained some experience in that area when he worked at a company that isolated natural products from the Asian rainforest. During his time there he was setting up enzymatic assays to screen these libraries to look at their effect on certain enzymes, which outcome is valuable for the cosmetic industry.
Joining the Carlson lab at Umeå University to solve viral structures
In December 2017, he defended his PhD at the University of Dundee and was eager to start the next chapter.
“I already knew I wanted to apply for the position in Lars-Anders's group in Umeå before my PhD defense, but I knew I had to finish first, then write my application in one day, because the application deadline for the postdoc position in Umeå expired the next day after my defense. This position seemed perfect, exactly what I wanted to do; combining infection biology and cryo-electron microscopy”, he explains.
By spring 2018, Karim was moving to Umeå and he couldn’t be happier for the opportunity. Lars-Anders recently established his lab, working on structure and mechanism of viral replication complexes and adenoviruses. Adenoviruses cause respiratory illness with flu- or cold-like symptoms. There are about fifty different types of adenoviruses which can infect humans. In children, symptoms appearing in the digestive tract can become life threatening.
The first collaborators of the Carlson group who Karim met early on were Professor Niklas Arnberg and Associate Professor Annasara Lenman from the Department of Clinical Microbiology.
“On the first day of my postdoc position, Annasara handed us a box full of viruses and said that these are the ones they would like to get to know their structures of. And we chose adenovirus F41, which structure we successfully deciphered within the next 2.5 years.”
Karim explains how grateful he is to his supervisor, Lars-Anders Carlson, and what an incredible teacher he is. He tells that in a matter of months, he learned his way around all aspects of cryo-electron microscopy; from sample preparation, to how to use the Titan Krios microscope and data processing. He highlights the fantastic, state-of-the art facilities in Umeå, especially the Umeå Centre for Electron Microscopy (UCEM), which was key for his research. After they published the structure of adenovirus F41, he jumped back to his initial project, which is the genome replication of alphaviruses, which may cause infectious arthritis, rashes or fever. For this project, they collaborated with SciLifeLab’s Human Antibody Therapeutics infrastructure unit in Solna to identify antibody fragments capable of targeting their protein of interest.
On the first of September 2023, Karim is starting his own research group at the University of Groningen, Netherlands. He explains that he is still going to be working on human adenoviruses to start with, but he wants to branch out to other viruses later.
“I am really excited to figure out more about how viruses alter mitochondrial function and how they hijack mitochondrial function to benefit their replication and how they then block innate immune signaling. And by doing so, it will be possible to identify novel host targets that can be drug targeted or develop drugs that break up the interaction between viral and host proteins”, he continues.
Karim is eager to work in an environment where he can learn from others and contribute to their work as well. At the University of Groningen, he will be placed at the Department of Molecular Pharmacology where researchers work on respiratory diseases. This is the perfect match for Karim since he is working with viruses causing respiratory disease, coming from chemistry, thus he has the opportunity to learn more about the biology of respiratory diseases from his new colleagues.
“Umeå is one of the best places to do science”
During his time at Umeå University, many people contributed to his research, and colleagues became good friends. Karim highlights what a fantastic work environment the Department of Medical Biochemistry and Biophysics is, and that Umeå has great research infrastructure, which all contribute to the special way of how science is done there.
“Science in Umeå is so inclusive and supportive! I did not experience this neither in Germany nor in the UK. The fact that you are somewhat isolated here makes people work more closely together. This is what science is about for me; working together in a great, more relaxed than stressful environment to answer the questions. If you can live with the darkness and cold, Umeå is one of the best places to do science and to see the northern lights from your living room window!”
He is especially thankful to his supervisor Lars-Anders Carlson and the Carlson lab, especially to Selma Dahmane, but also to collaborators and peers for great conversations and working together, such as Niklas Arnberg (Dept. of Clinical Microbiology), Annasara Lenman (Dept. of Clinical Microbiology), Ronnie Berntsson (Dept. of Medical Biochemistry and Biophysics), Magnus Wolf-Watz (Dept. of Chemistry), André Mateus (Dept. of Chemistry), Gerhard Gröbner (Dept. of Chemistry), Paulina Wanrooij (Dept. of Medical Biochemistry and Biophysics) and Erik Johansson (Dept. of Medical Biochemistry and Biophysics), among others.
Karim also emphasizes how instrumental the connections and opportunities through the Laboratory for Molecular Infection Medicine Sweden (MIMS) and the Nordic EMBL Partnership, along with Umeå Centre for Microbial Research (UCMR), were in advancing his career. Participating at international and national conferences, seminars, academic dialogs with local and invited researchers, play a vital role in reinforcing the robust research environment and scientific community in Umeå.
“What MIMS with the Nordic EMBL Partnership, and UCMR mean to Umeå and bring to Umeå, is what I benefitted from the most. MIMS and UCMR create such a strong hub for infection research, it had a massive influence on me and my career.”
There are numerous roads to take leading to become a successful researcher
Finally, Karim shares his insights based on his personal experience with those who think about a scientific career. He emphasizes that academic performance in high school does not always reflect one's intelligence or abilities. It takes time to explore and find one's passion as there are many paths to success. If you are an undergraduate or graduate student, it is better to be honest with yourself about whether a particular degree or program aligns with your interests and goals. It's never too late to change course and pursue something that genuinely excites them.
“In the world of science, collaborations can be incredibly valuable for learning and making progress in research. It's important to seek out collaborations with colleagues in different fields, and to attend seminars and other events to continue learning and growing. After PhD, or even as a postdoc, it is okay to leave academia if it's not the right fit for you. Teaching or working in industry can be just as rewarding and scientific. If I would be to leave science completely, I would become a chef and my special dish would be pumpkin gnocchi, which I learned from my mom, who is an excellent cook.”