We are globally interested in how organisms adapt to different environments. Our study system is the African trypanosome parasite, which cycles between a tsetse fly vector and a mammalian host. In humans and animals, the parasite causes a fatal disease called African trypanosomiasis (sleeping sickness). In order to adapt itself from living in the bloodstream to living in the fly, the parasite must change the transcript levels of thousands of genes in the genome. We want to know more about the molecular mechanisms behind these changes.
In this project, we’d like to identify factors that are important for remodeling the parasite surface, which is important for immune evasion in the mammalian host. In the mammalian host, parasites constantly change the proteins on their surface to evade the host immune system. Upon transfer to the fly, a new invariant protein coat replaces the varying one. We want to know what proteins are important for this replacement. We have replaced the gene that codes for the fly-specific parasite coat with a gene for Green Fluorescent Protein (GFP). This way, we can quickly identify any parasite that has remodeled its surface proteins to live in the insect. To identify new factors that are important for this surface remodeling, we will take advantage of a collection of ~7000 plasmids, each of which has a parasite gene that can be overexpressed when introduced into a parasite. We will screen this collection of plasmids to try and identify genes that induce surface protein remodeling. Techniques that will be used in this project include sterile parasite culture (equivalent to tissue culture for mammalian cells), flow cytometry, and genetic modification of the parasite genome.
To complete your application for summer research in Biology, please contact me to discuss the project and submit this google form https://docs.google.com/forms/d/e/1FAIpQLSeqM501OJDhyHqTWfLEaYw44MNJKvUkvL7VXZ9s1Te04C2B3g/viewform by Feb 28. Please note that this project is only available as an in person project; it cannot be done remotely.
We aim to understand how parasites adapt to different environments in the fly and mammalian bloodstream, with an eye toward manipulating this adaption to help fight human disease. African trypanosomiasis affects the rural poor, and new drugs are urgently needed. However, drug companies are not highly motivated to produce drugs for people that can’t pay for them. We hope that by understanding more about parasite adaption, we can improve the lives of many living in regions of Sub-Saharan Africa where African trypanosomiasis is endemic.