Janelle Sauvageau
Title: Harvesting the potential of glycans for treating and preventing diseases
Abstract: Glycans have been used in vaccines and in therapeutics to treat or prevent diseases since many years. Streptomycin is in the clinic since the 40s to treat tuberculosis infections and the pneumococcal vaccine is now containing 23 different purified capsular polysaccharides, and both are still administered today to patients. NRC has a rich history of developing carbohydrate therapeutics and vaccines, and today many projects supported by NRC are still involving glycans and carbohydrates. During this webinar, I will first describe the work surrounding the development of a potential HIV latency reversal agent that I currently lead. Next, I will recount the synthesis of a novel pentasaccharide for glycoconjugate production. This is a potential prophylactic vaccine candidate against Pseudomonas aeruginosa, an antibiotic resistant bacteria. Finally, I will discuss the implications of glycan content in glycoprotein therapeutics and the analytical methodologies that have been developed to interrogate that. Overall this talk will provide a brief overview of three glycan related projects of interest to NRC.
Bio: Dr. Janelle Sauvageau is trailblazing biological chemistry within the Human Health Therapeutics Research Centre at the National Research Council (NRC). Her career began at the Université Laval in 2001, achieving a B.Sc. and M.Sc. in Chemistry. Before her Ph.D., she worked in Bremen, Germany, as an Analytical Chemist for the Center for Environmental Research and Environmental Technology, then Wellington, New Zealand as a Researcher for Industrial Research Limited. Dr. Sauvageau stayed in New Zealand to pursue her Ph.D. at Victoria University of Wellington graduating in 2013. She was brought back to Canada by the NRC in late 2014 to work in the field of vaccines and immunomodulators.
At the NRC, Dr. Sauvageau’s interest switched to a new Pathogen Associated Molecular Patterns (PAMPs) molecule excreted by a gram-negative bacteria and its impact on the immune system. In vivo, these PAMPs are produced in many antimicrobial resistant bacteria (e.g. Neisseria gonnorheae) and can activate HIV in cell models. She synthesised heptose phosphates derivatives, which were key in defining the specificity of the TIFA axis. Her works shows that these new PAMPs could be a latency reversal agent and thus a cure for HIV.
She also contributed to the development of a vaccine against Pseudomonas aeruginosa to prevent infections in cystic fibrosis patients and other immunocompromised individuals. Usually, the glycans for these vaccines are extracted from bacterial biomass, but this proved too challenging for this particular glycan. Her contribution was critical the development of this vaccine and evaluation of the most effective chain length for immunogenicity.
Her study of the surface glycans of pathogens also forms part of national efforts against COVID-19. Recently the assays she developed, simplified and sped-up the analyses of glycans on SARS-CoV-2 glycoprotein vaccine antigens. When time is of importance, for example such as in a pandemic, those assays will be critical to develop vaccines faster as current analyses are so time consuming that they slowed down the glycoprotein vaccine development process during the COVID-19 pandemic.
Despite her early career stage, Dr. Sauvageau’s efforts have been recognized with 4 patents, 602 citations, as well as several grants and awards such as the ACS Early Career Investigator Award and an NRC Ambassador award (2018). She has also been invited to deliver presentations at international and national conferences including the ACS Early Career Investigator Symposium and the Canadian Glycomics Symposium.
Dr. Sauvageau is also engaged in mentoring activities, and the promotion of policies for equity in science careers. She recognized the need for young researchers to have their own support network, so she worked within the NRC to establish the Early Career Network. One of her key activities in the ECN was to create a ECR group within her research center. She is also actively involved in supporting equity diversity in inclusion by performing research on differential access to resources for equity-deserving groups. Her work informs policies within the whole NRC.
Seyed Amirhossein Nasseri
Title: Not all glycosidases follow Koshland mechanisms: A functional metagenomic screen in search of unconventional glycosidases
Abstract: The vast majority of the glycosidases characterized so far follow a variation of a common mechanism, known as Koshland mechanism, to hydrolyze the glycosidic bonds. The sheer number of uncharacterized genes in bacterial genomes however, encouraged us to explore whether other enzymes might be present in nature, that follow distinct mechanisms for breaking glycosidic bonds.
We therefore developed a novel screening strategy that selectively identifies unconventional glycosidases and then performed a screen of a human gut microbiome metagenomic fosmid library using our strategy in search of novel glycosidases. This led to the identification of a dozen fosmid hits that do not encode any known glycosidases.
We have followed suit with studying the identity of the individual genes that are responsible for the observed activities and now have some early insights into the possible mechanism of action of some of our hits. This study will therefore shed light on the various mechanisms that nature is employing for hydrolysis of glycosidic bonds. In addition, the number of unknown hits that we discovered in a very well-studied biological system, the human gut-microbiome, strongly suggests that many more interesting enzymes with diverse mechanisms are waiting to be discovered in other lesser studied environments.
Bio: Seyed Amirhossein Nasseri obtained his bachelor’s degrees in Chemistry and Chemical engineering from Sharif University of Technology, Tehran, Iran, and is now a PhD candidate in Withers group, Department of Chemistry, University of British Columbia.