PhD studentship on Babesia TSR proteins
Babesiosis is a disease symptomatically very similar to malaria, caused by Babesia parasites infecting and multiplying in erythrocytes. Babesia and Plasmodium are closely-related protozoan parasites. Both are transmitted by insect vectors. Babesiosis affects a large range of vertebrates including livestock, companion animals, and also humans. In animals Babesia infections are frequently fatal if left untreated and cause a significant economic burden. Babesiosis in humans is a zoonotic disease. The disease is mostly asymptomatic and only fatal in immune-compromised or elderly individuals. However, numbers of human babesiosis cases are rising, especially in the USA where this parasite is the most common transfusion-transmitted pathogen.
All symptoms of this disease, and onward transmission result from the cyclical invasion of host erythrocytes, and thus a better understanding of this process could yield vital new drug or vaccine candidates. Whereas this process is well-studied for malaria parasites, little is known about this process in Babesia. Proteins in specialised organelles called micronemes are required for host cell recognition and parasite motility. Thrombospondin type 1 repeat domain (TSR) proteins form an important group of micronemal proteins in Plasmodium and have critical roles in motility, invasion of salivary glands, hepatocytes and erythrocytes. Some TSR-containing proteins recognise glycosaminoglycans on the host cell surface and at the same time connect to the actin-myosin motor through their cytoplasmic tail, generating the motility required for host cell invasion. One such example is the thrombospondin-related anonymous protein (TRAP). Four TSR-domain containing proteins can be identified in the B. divergens genome. Based on limited transcription profiling all four genes appear expressed in blood stages of Babesia. Three of these hypothetical proteins are secreted TSR-proteins, one of which is showing domain structures reminiscent of TRAP. We hypothesise that similar to Plasmodium, TSR-proteins are involved in and required for erythrocyte invasion of B.divergens.
This project will study the role of B. divergens TSR-proteins in erythrocyte invasion to understand the steps leading to invasion and to rationalise their use as vaccine candidates.