McGill’s annual Biochemistry Research Awareness Day (RAD), hosted by the Biochemistry Undergraduate Society (BUGS), took place on the 15th of November this year. RAD 2014 provided students with an opportunity to hear professors in their faculty present their research and discuss ways for students to become involved in undergraduate research at McGill University. After the presentations, students were able to meet and talk with the professors in small groups to learn more about their work.
First to present was Dr. Albert Berghuis, Professor and Chair of the Department of Biochemistry at McGill University. He spoke about the issue of dramatic increases in antibiotic resistance, and the use of structural data as a strategy to combat superbugs and antibiotic resistant enzymes. Citing recent examples such as the often untreatable C. difficile bacteria which ravaged through the country just last year, his speech acted as a reminder of the ever-pressing need for novel treatments against pathogenic bacteria. Current ongoing research in the Berghuis Lab includes the study of various drug-binding mechanisms and antimicrobial agents, with structural biological approaches such as X-ray crystallography and nuclear magnetic resonance spectroscopy, often in collaboration with researchers from other Canadian universities.
Next to speak was Dr. Morag Park, Director of the Rosalind and Morris Goodman Cancer Research Centre. Her presentation focused on the role of tyrosine kinase Met receptors in basal-type breast cancers, as evidenced by their over-expression in cell-signalling pathways in murine models, as well as multiple pathologies in MMTV (Mouse Mammary Tumour Virus)/ Met mice, characteristic of human breast cancers. Research in the Park Lab (often in conjunction with the Hallets Lab, which focuses on breast cancer informatics) aims to identify signal transduction pathways in cancers, as well as the regulation and integration thereof, in order to better understand tumour cell induction, invasion, and metastasis.
The Goodman Cancer Research Centre (GCRC) is a world-renowned research facility affiliated with McGill University’s Faculty of Medicine, and has for many years allowed McGill’s graduate students to conduct independent studies in cancer research with the world’s top scientists and research fellows.
The next speaker was Dr. Kalle Gehring, head of the McGill NMR Lab, presenting a brief introduction to the application of Nuclear Magnetic Resonance (NMR) spectroscopy in the study of protein and nucleic acid structures. Recent research in the NMR Lab has included the study of nucleic acid hairpins and various PolyA binding proteins.
Dr. Gehring also spoke at length regarding the importance of undergraduate research and the many opportunities here at McGill University, citing examples of typical research projects and topics as well as published student works—including past papers published in MSURJ (the McGill Science Undergraduate Research Journal), affiliated with the NMR Lab. Also mentioned were summer research grant opportunities such as NSERC, Bionano, FRQ, and the annual GRASP symposium.
(The NMR Lab is currently recruiting—according to Dr. Gehring, undergraduates joining before December 15 will be cordially invited to a LaserQuest battle, where they will be welcome to shoot at professors as they please.)
Also representing the Goodman Cancer Research Centre was Dr. Sidong Huang, Assistant Professor at McGill and the Canadian Research Chair in Functional Genomics. Speaking on the topic of Functional Genomics to Guide Cancer Therapy, Dr. Huang cited the use of tools such as high-throughput RNA interference screens in his laboratory to study cancer-relevant pathways (e.g. the effects of inhibitor regulation in cancers like BRAF-mutant melanoma), identify novel genes and networks and eventually overcome drug resistance in cancer therapy.
Speaking on behalf of Dr. McInnes, research associate Dr. Diez laid out the projects going on at the McInnes lab. Located in the Lady Davis Institute of the Jewish General Hospital, the lab is currently looking for two undergraduate students passionate in biochemistry research. Dr. McInnes’ early work involved the development of the mammalian retina, specifically, the hundreds of genes that when mutated produced a condition known as retinitis pigmentosa, which involves the death of photoreceptor cells in the retina. From this research, the lab began examining a specific gene that was expressed over 100-fold in retinal tissue. Using an animal model, they proceeded to delete the gene in mice and found that this caused the mice to die as soon as they were born. Intrigued at the potential developmental possibility of the gene, they continued to examine the fetuses for clues as to the gene’s function, and found abnormalities in the brain called focal neuronal ectopias, which detail an overmigration of neuronal precursors in the brain. Being the first lab to work on this gene, there is still a lot of progress to be made concerning its function, and future paths include working with proteins that interact with the gene and developing a conditional knock-out in mice.
The Nepveu lab studies DNA damage response in the context of cancer. The DNA damage response begins when damage is detected in cells which triggers a series of modifications on proteins leading to the activation of certain processes including chromatin remodeling, transcriptional regulation, DNA repair and a halt in cell proliferation. Cancer cells need extremely efficient DNA repair mechanisms because they must proliferate extensively to resist chemotherapy, as the treatment aims to kill cells by causing an excess of DNA damage. The focus of Dr. Alain Nepveu’s studies is on genes that are haploinsufficient tumour suppressors, which are overexpressed in advanced cancer. Using transgenic mice models, tumour development is followed and analyzed for changes in genetic material. Recruitment of proteins is monitored through expression of fusion proteins with Green Fluorescent Protein (GFP), and in vitro cells are filmed in order to monitor their DNA using TimeWarp analysis. Eventually the garnered results are compared to what happens in real cancer patients, with the hope of advancing the knowledge of the DNA repair mechanism in tumour cells.
Following on the theme of cancer research, Dr. Maxime Bouchard’s lab examines the development of the embryonic urogenital system and how these pathways are reproduced in cancer cell behaviour. The elongation of the ducts of the renal and genital system in embryos involves the invasion of surrounding tissue by tip cells, which happens in a group migration. It was previously thought that these cells were static and interconnected, however they now appear to be in fact moving around and “floating together”, much like metastatic cells. This new field of research integrates embryonic developmental processes and cancer cell biochemistry, and has a promising future.
The main area of interest in Dr. Arnim Pause’s lab involves working with tumour suppressor genes – one which works specifically to treat the Birt-Hogg-Dubé syndrome, and another which is frequently deleted in a range of cancers. Birt-Hogg-Dubé syndrome is a very rare autosomal dominant hereditary disorder which predisposes the affected patient to a number of tumours, including hair follicle tumours, lung and kidney cysts and renal and colon cancer. It occurs when there is a mutation in the FLCN gene responsible for coding a protein known as folliculin. Using mice and C. elegans as models, the study of the FLCN gene and specifically its loss of function is one of the projects undertaken in this lab. A second endeavour involves exploring the Histidine-Domain-Protein-Tyrosine-Phosphatase (HD-PTP) protein, of which the chromosomal region 3p21.3 is a tumour suppressing gene. HD-PTP itself forms a complex which is involved in the endosomal trafficking of cell surface receptors, and this is guided by an ESCRT complex. Using a mouse model, the lab is looking at further revealing this protein’s function in the development of tumours.
Dr. Martin Schmeing’s research focuses primarily on the structure and function of large molecular machines in carrying out vital cellular processes. His lab uses two structural techniques, x-ray crystallography and single particle electron microscopy, as well as many biophysical and biochemical techniques. These methods allow for pictures to be taken of extremely small particles performing cellular activities, and can be pieced together to show the mechanism of a certain biological process. Dr. Schmeing showed an example of this in a short video about ribosomal translation. Currently, one of Dr. Schmeing’s main investigations is concerning non-ribosomal peptide synthesis, another mechanism that makes proteins. This process is carried out by enzymes known as Non-Ribosomal Peptide Synthetases (NRPSs), which are very large and have a complex assembly line mechanism. Antibiotics are indispensable in the study of non-ribosomal peptide synthesis as many of their proteins are produced by this mechanism.Gaining a better understanding of this process could lead to quicker synthesis of antibiotics by modifying and improving the efficiency of these enzymes. A recent success in Dr. Schmeing’s lab was the solution to the domain configuration of F-A didomain.
The research performed by Dr. Michel L. Tremblay encompasses many different areas of science, including oncology, microbiology, immunology, and experimental medicine. He also studies gene and stem cell therapies with Dr. Jerry Pelletier at McGill. Dr. Tremblay’s main area of research concerns the understanding and manipulation of protein tyrosine phosphatases (PTPases) in normal and disease conditions. Many PTPases are in fact activating enzymes; half of the 109 PTPases in the human genome are oncogenic proteins. Dr. Tremblay says that, including all the bacterial, viral, and parasitic elements, there are “over 3000 protein tyrosine phosphatases, many of [which] will be outstanding targets for drugs”. His lab does work on phosphatomics, and has identified two novel phosphatases in the human genome. This information can be found on their website. Additionally, Dr. Tremblay does further research surrounding the genomics of disease.
Dr. Jason Young’s lab investigates how functional polypeptides are made in cells. This requires the proper folding of proteins, which is carried out by molecular chaperones. Chaperones have many other functions, including moving proteins through the cell and pulling apart proteins when they aggregate. They have a role in processes such as aging and oncogenesis. The chaperone that is investigated in Dr. Young’s lab is Hsp70, which Dr. Young called “a deceptively simple system”. Hsp70 is regulated by co-chaperone proteins, many of which are from the DNAJ family, that activate Hsp70 to bind polypeptides. They used “a structure based design approach to develop new inhibitors of Hsp70”, which could be useful in targeting cancerous cells, as they are especially dependent on chaperones. This also has applications in misfolding diseases such as cystic fibrosis. Currently, they are addressing how the Hsp70 system interacts with the Hsp90 system to assist in folding.
Dr. Young also spoke about the benefits of participating in undergraduate research, emphasizing on the importance of practical experience. Lab participation allows extended practice in performing key lab techniques and skills important for science-related work, whereas most lab courses last an average duration of a few weeks. Getting involved in research also helps to improve analytical and presentation skills important for future papers and seminars, and introduces students to the research community, allowing exposure to professors, graduate students, postdoctoral scholars, and more. Dr. Young encourages interested students to inquire about summer research positions early (December/January), as many labs plan several months in advance.
To wrap up the presentation portion of the event, a number of other guests took the floor to speak about exchange opportunities involving research:
Representatives from Sanofi Pasteur, a division of the multinational pharmaceutical company Sanofi, introduced a co-op program that involves working with their company for 8-12 months. Two students from the University of Strasbourg in France also spoke about their experience with the exchange program—The University of Strasbourg is one of the top research universities in the country, and this exchange is a great opportunity to earn credits while studying abroad.