Nicolas Grinberg - Department of Chemistry

My name is Nicolas Grinberg and I am a Honors Chemistry student at McGill University. During my honors' research project at McGill, I did a project involving the use of Hydrogen-Deuterium Exchange Mass Spectrometry, a biophysical method to understand the dynamics of a flexible enzyme. At the end of the project, I wished to learn more biophysical techniques to answer the kind of questions my project focused on. On a less technical level, I also wanted to broaden my horizons by working abroad for a short time and discovering new ways of thinking and solving problems. In this context, I had the privilege to be awarded a Schull-Yang International Experience Award to finance a twelve-week research internship in Mainz, Germany, in Summer 2019. Without Mr. Schull and Ms. Yang's generous support, this experience would simply not have been possible. Besides the evident living expenses, the award so generously given allowed me to go regularly to Frankfurt for work. This has truly been an amazing summer, which has broadened my knowledge in the field of protein chemistry.  

 

Mainz is the capital of the German state of Rheinland-Palatinate. It is part of a highly-industrialized and innovative network of cities along the river Rhine. Universities in the area, like the Johannes Gutenberg University where I worked in the biochemistry department, are all highly integrated and collaborate very strongly with one another. I chose this group as they specialize in NMR spectroscopy, a powerful biophysical technique to analyze protein folding and how they behave with interaction patterns. Having lived in Canada, where larger cities are very far apart, I was happy to discover this cosmopolitan and highly collaborative environment between Rheinland universities. As part of the learning experience, I was invited to several conferences by the laboratory director, Dr. Hellmich. Along with several groups in our institute and in nearby Goethe University, we were studying a class of membrane proteins known as Transient-Receptor Potential Receptors, which are involved in a plethora of sensory and stimuli-response functions. This family of receptors has been involved in everything from pain sensation to heat sensation. They have been linked to several fatal genetic diseases such as Marie-Tooth syndrome. The protein has a region known as the intrinsically disordered region (IDR). It has been shown that the region interacts with lipids in the cell membranes. The details of this interaction are quite nebulous and are the root cause of several fatal diseases such as congenital distal spinal muscular atrophy.  

 

My first job as a biochemistry student was to purify the protein domain of interest. This was done by cloning a plasmid coding for the IDR into E. Coli bacteria. After growing the bacteria for a day, the cells were harvested and the protein was isolated. Once purified, I would go with my mentor Benedikt to our collaboration partners in Frankfurt to take NMR measurements. The technique has been widely used by chemists for decades to analyze small molecules. It uses powerful electromagnets to probe the electronic environment of an atom. Most atoms behave like magnets and have a magnetic dipole moment. This magnetic dipole moment is highly dependent on the environment an atom is in. As a chemist by training, I was good at understanding this technique as it is used a lot in organic and quantum chemistry, two of my favorite topics. I was, however, very eager to learn how to use it in the context of protein chemistry. Using the technique, we were able to account for all of the atoms in the region. With our partners in Frankfurt, we were able to account for the dozens of amino acids in this region and better understand how they interact with membrane lipids. We analyzed several mutants of these disordered regions and used the technique to understand which parts of the protein moved when activated by peptide. After the data was gathered, I spent the best part of the summer processing the data with the help of my mentors. I learned how to use NMR data from Carbon, Nitrogen and Oxygen from the protein backbone to determine how the protein and its mutants behave in the presence of lipids. This part was my favorite, as I was able to use my training in Quantum Chemistry to understand how atoms behave in response to magnetic fields to answer fundamental questions in how this system behaves.  

 

Summer 2019 was truly an amazing learning experience. While being exposed to a highly collaborative environment, I was exposed to new ways of thinking and engaging in scientific discourse. It is here that I was able to intersect concepts that I learned in my undergraduate such as NMR with complicated biological problems in membrane chemistry.