Researchers at the Laboratories have been funded by grants from DNDi, NIH, NSF, WHO, Drugs for Neglected Diseases, Bill and Melinda Gates Foundation, and The Alternative Research and Development Fund; as well as through collaborations with established and newly founded pharmaceutical firms including Marion Merrell Dow, Scynexis LLC., Genzyme, and Fraunhoffer LLC.
Dr. Nigel Yarlett’s group is engaged in research centered on evaluating the genomic changes occurring in the intestinal parasite Cryptosporidium parvum grown in vitro using a hollow fiber bioreactor, which was developed at the laboratory (funded by the Bill and Melinda Gates Foundation). Cryptosporidium hominis and C. parvum cause diarrheal disease which can be life threatening in infants and immunocompromised individuals. Infant survivors often suffer from stunted growth and cognitive impairment. All cryptosporidium species harbor a dsRNA virus whose role in the disease pathology has not been determined. Part of the research is aimed at determining the contribution of the dsRNA cryspovirus to cognitive impairment and stunted growth in infant survivors (funded by Grand Challenges). We have also developed an in vitro culture method enabling complete life cycle stages of Toxoplasma gondii to be accessed, using a bioreactor containing synthetic (non-animal products) (funded by Alternative Research and Development Foundation). Part of this research is aimed at determining the role of polyamines in ‘persister’ stage formation by Toxoplasma gondii. My group is also collaborating with Dr Linda Carozza to determine the precise role of polyamines in the development and onset of autism spectrum disorder.
Dr. Cho Chan’s research is broadly interested in the role of amyloids in cell adhesion proteins that mediate pathogen-host and pathogen-environment interactions. Microbial interactions with their environments and other microbes through cell surface proteins are important for proliferation and survival. Recent work is centered on the understanding of force-induced activation of amyloid nanodomains in yeast adhesion proteins using different biochemical techniques. The research group integrates molecular, chemical, and functional analyses to develop and understand how forces in the microbial environment affect the adhesion proteins on the cell surface. Mechanical force increases the propensity for binding through the formation of amyloids in yeast adhesion proteins. This mechanism is important in understanding how microorganisms form stable biofilms or adhere to other surfaces or proteins even under harsh environmental conditions.
Fatty Acid Reactions
Dr. Rita Upmacis’s research focuses on the interaction of fatty acids with reactive oxygen and nitrogen species in inflammation and disease, as well as the synthesis of new transition metal complexes displaying novel structures. Some of the fatty acids explored include prostanoids, which are a family of lipid mediators formed from arachidonic acid by the action of cyclooxygenase enzymes and serve as biomarkers of vascular function and inflammation. There may be sex-dependent differences in prostanoid production, indicating that males and females require different therapeutic approaches during disease but historically, medical studies have neglected the examination of females. Studies investigate sex-dependent differences in samples employing techniques such as enzyme immunoassays and gas chromatography-mass spectrometry. In separate studies, novel transition metal complexes incorporating nitrogen-containing ligands, such as metronidazole (an important antibiotic and antiprotozoal medication), are synthesized, characterized and potentially explored as antimicrobials.