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 are interested in understanding what happens to chromatin interacting proteins when parasites adapt to a new host. Chromatin is made up of DNA and proteins around which the DNA is wrapped. We have previously showed that chromatin interacting bromodomain proteins are essential to maintain immune evasion for parasites living in the mammalian bloodstream. We would like to know what happens to these proteins as parasites adapt from living in the mammalian bloodstream to living in the insect. In particular, we want to know if they change their location on the DNA. To investigate this, we will use a technique called Cleavage Under Targets and Release Using Nuclease (CUT&RUN) which takes advantage of high-throughput sequencing to produce genome-wide mapping of bromodomain protein binding on the DNA. This project contains a bench science component (preparing samples for high-throughput sequencing) and a computational component (analyzing the sequencing). Additional computational analysis of transcriptome changes that occur following bromodomain inhibition may also be a component of the project. Bench science techniques that will be used in this project include include sterile parasite culture (equivalent to tissue culture for mammalian cells), flow cytometry, and CUT&RUN. Computational techniques include installation of high-throughput sequencing analysis software, shell scripting, python programming, and possibly some R.
To complete your application for summer research in Biology, please contact me to discuss the project and submit this https://docs.google.com/forms/d/e/1FAIpQLSeqM501OJDhyHqTWfLEaYw44MNJKvUkvL7VXZ9s1Te04C2B3g/viewform by Feb 28. Please note that this project might only be available as an in person project.
We aim to understand how the 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.