A 2023 Crick PhD project with Adam SaterialeProject background and descriptionCryptosporidium, or ‘crypto’, is an intracellular parasite that causes a severe diarrhoeal disease known as cryptosporidiosis. Crypto infection accounts for over 200,000 deaths per year and even mild cases are linked to growth stunting and impaired cognitive development in children. Despite this significant impact on global health, very little is known about crypto infection and the host immune response (for a brief overview of the significance of crypto research, see [1]). Our lab studies this interplay of virulence and immunity using a recently isolated species of the parasite that naturally infects mice, Cryptosporidium tyzzeri [2]. This mouse model of cryptosporidiosis closely resembles human infection in location, resolution, and the associated disease pathology. Further, the C. tyzzeri genome can be easily manipulated using CRISPR based editing [3]. Put simply, this new model of infection gives us full control over BOTH host and parasite genetics, which we are leveraging to answer fundamental questions about host-pathogen interactions: How does the immune system recognize and respond to a crypto infection? What host genetic factors predispose one to a severe infection? How do they function? How does the parasite evade detection and suppress host immunity? What parasite genetic factors are associated with highly virulent strains? How do they function? To answer these questions, we use a combination of genetic screens and targeted crosses to identify genomic loci that correlate with resistance (host) and virulence (parasite). We then employ a variety of genetic and chemical tools to drill down the molecular mechanisms at play. Candidate backgroundWe are interested in candidates with a strong interest in infectious disease and a desire to work on projects that bridge virulence and immunity. Projects in my lab generally involve super resolution microscopy, high-throughput sequencing, bioinformatics, CRISPR driven genetic manipulation, and basic molecular techniques. Expertise in these areas is beneficial, but certainly not a pre-requisite. References1. Striepen, B. (2013) Time to tackle cryptosporidiosis. Nature 503: 189-191. PubMed abstract 2. Sateriale, A., Šlapeta, J., Baptista, R., Engiles, J.B., Gullicksrud, J.A., Herbert, G.T., . . . Striepen, B. (2019) A genetically tractable, natural mouse model of Cryptosporidiosis offers insights into host protective immunity. Cell Host & Microbe 26: 135-146 e135. PubMed abstract 3. Vinayak, S., Pawlowic, M.C., Sateriale, A., Brooks, C.F., Studstill, C.J., Bar-Peled, Y., . . . Striepen, B. (2015) Genetic modification of the diarrhoeal pathogen Cryptosporidium parvum. Nature 523: 477-480. PubMed abstract |
