Human African Trypanosommiasis (HAT, sleeping sickness) and Animal African Trypanosomiasis (AAT, Nagana) are fatal, tropical neglected diseases in Sub-Saharan Africa, caused by the African parasite trypanosoma. It is estimated that annually 10-30 thousand individuals, as well as more then 3 million domestic and wild African animals are affected by HAT and AAT. Trans-sialidase (TS) are expressed by trypanosomes and represent a major virulence factor in HAT and AAT. They depict an unusual class of glycosyltransferases, catalysing the reversible transfer of preferentially α2,3-linked sialic acids (Sia) to terminal β-galactose residues on acceptor glycoproteins of the parasite’s surface. This newly formed negatively charged surface coat is known to play a fundamental role in several biological processes during the life cycle of trypanosomes in host and vector and secures their survival in both.
Biologic functions of trans-sialidase from Trypanosoma congolense and their role in parasite
Development and survival in host and vector
In this project we focus on the biochemical characterisation of Trypanosoma congolense (Tcon) TS including its mode of carbohydrate recognition, catalytic Sia transfer as well as ligand specificity and binding kinetics employing a variety of biophysical and -chemical methods, in order to obtain further insights into structure function relationships and their biological functions. To tackle these scientific objectives we have established highly interdisciplinary collaborations with scientist from different research fields including sialoglycobiochemistry (CBIB, University of Bremen), NMR (Institute for Glycomics, Australia), parasitology (Liverpool school of tropical medicine, United Kingdom), immunology (University of General San Martin, Argentina) molecular cell biology (University of Würzburg, Germany), trypanosoma biology (AC-NTDFB, Nigeria) and marine glycobiochemistry (MARUM, Uni Bremen), providing an excellent scientific environment. In-depth knowledge on TconTS and its biological functions will pave the way for the design and synthesis of novel specific and highly potent trypanosomal TS inhibitors that might be used as antiparasidal drugs in the future, in order to control trypanosomiasis in affected
Dr. Mario Waespy (CBIB)
Prof. Dr. Sørge Kelm (CBIB)
Dr. Frank Dietz (CBIB)