Students work with biochemistry, biology, and chemistry faculty on research with state-of-the-art equipment, and are often invited to be co-authors on articles published in academic journals.
Thesis: "Identification of genes involved in Helicobacter pylori glycolipid and glycoprotein biosynthesis"
Abstract: Helicobacter pylori is a gram-negative disease-causing bacterium that been linked to gastric carcinoma, and infection often leads to chronic gastritis and ulcers that can last for a lifetime if left untreated. Current efforts to cure H. pylori infection requires “triple therapy”. There is an urgent need for new therapeutics as increasing resistance to triple therapy has developed. H. pylori’s cell surface is decorated with highly ordered glycan structures containing unique monosaccharide building blocks that are critical for its virulence, therefore, bacterial glycans are attractive therapeutic targets. However, the genes responsible for the biosynthesis of glycosylated proteins and lipids in H. pylori are not fully known nor characterized. Recent work in our laboratory has shown that glycoprotein and glycolipid biosynthesis appear to occur via a shared lipid-carrier-mediated pathway that bifurcates. Therefore, in this study, we probed our working model of glycoprotein biosynthesis via construction of glycosylation mutants coupled to metabolic oligosaccharide engineering (MOE) to study glycan production. Our results identify additional genes involved in glycolipid and glycoprotein biosynthesis and allowed us to refine our working model of these overlapping pathways. Ultimately, this work has the potential to reveal targets for glycan-based antimicrobial interference strategies.
Most memorable biochemistry class: Biochemistry and Cell-biology with Bruce Kohorn
Currently: After graduating in May of 2022, I have been trying to enjoy the summer with friends and family and catch up on four years of sleep!
Thesis: Bacterial Coat of Armor: Probing how Glycan Biosynthesis in Helicobacter pylori Modulates Host Immune Recognition
Abstract: Helicobacter pylori is a gram negative, pathogenic, and opportunistic bacterium that is known to colonize more than 50% of all human gastrointestinal tracts. H. pylori is an alarming bacterium in the medical field due to its increasing antibiotic resistance rate. Cell surface bacterial glycans offer a unique potential target for new antibiotic therapeutics against H. pylori. These glycan structures and other molecules help create a sugar coat around H. pylori allowing the bacterium to evade the host’s immune system. The goal of this project is to assess the extent to which disruption of glycan biosynthesis in H. pylori modulates host immune recognition of the bacteria. Toward this end, the ability of human gastric adenocarcinoma cells (AGS) to recognize and respond to wild type (WT) H. pylori versus glycan biosynthesis mutants was compared by measuring AGS viability and expression of the cytokine CXCL-8 upon co-culturing with bacteria. In parallel, Thp-1 monocyte derived dendritic cell (DC) maturation rates were investigated after coculturing DCs with either WT H. pylori or glycan biosynthesis mutants. CXCL-8 expression was significantly diminished when AGS cells were cultured with the H. pylori glycosylation mutants compared to the WT. Additionally, DC maturation rates were significantly lower when DCs were exposed to the H. pylori glycosylation mutants compared to the WT. These preliminary results suggest that disruption of H. pylori glycan biosynthesis make the bacterium less immunogenic. Thus, the cell surface glycan structures on H. pylori appear important for immune recognition and response.
Most memorable biochemistry course: Advanced Cell and Molecular Biology with Bruce Kohorn
Since graduating: I am preparing to start a PhD program in biology at MIT in September where I hope to specialize in cancer immunology.
Thesis: "Metabolic Glycan Labeling in Bacteria Using Rare Azido L-Sugars"
Abstract: The rapid rise of antibiotic resistance demonstrates the ineffectiveness of existing antibiotics. Bacterial glycans are compelling therapeutic targets as they link to pathogenesis and contain rare monosaccharides absent from human cells. However, the systematic study of bacterial glycans remains challenging due to the presence of exclusively bacterial sugars which hamper traditional glycan analyses. Thus, the development of chemical tools to study bacterial glycans is a crucial step toward understanding and altering these biomolecules. This project employs metabolic oligosaccharide engineering to accelerate the investigation of bacterial glycans bearing rare deoxy amino L-sugars. Briefly, azide-containing analogs of N-acetyl L-pneumosamine, N-acetyl-L-quinovosamine, N-acetyl L-rhamnosamine, and N-acetyl L-fucosamine were screened for metabolic incorporation into glycans in a range of pathogenic and symbiotic bacteria. L-sugar analogs were narrowly incorporated into select pathogenic species that reportedly express L-sugar presenting epitopes, namely Plesiomonas shigelloides and Vibrio vulnificus. Surprisingly, L-sugar analogs were also utilized by the pathogen Campylobacter jejuni despite having no previous reports of L-sugar-containing glycans in this species. In contrast, the gut symbiont Bacteroides fragilis did not exhibit any appreciable utilization of L-sugar analogs. Distinct strains of L-sugar bacteria displayed diverse azide-labeled glycan profiles. Finally, azido sugars selectively labeled glycoproteins in P. shigelloides and V. vulnificus. Further application of metabolic probes based on rare sugars will refine our knowledge of glycans in diverse bacteria and aid the design of novel antibiotics.
Most memorable biochemistry classs: Chemical Biology
Since graduating: Currently I'm staying on campus for the summer to do research with Professor Danielle Dube. My research essentially extends on my honors thesis and I also train new students in the lab. My next plan in the fall is to pursue a PhD in chemistry at the Max Planck Institute of Colloids and Interfaces in Potsdam, Germany.