Objective
The parasite Trypanosoma cruzi is the etiological agent for Chagas disease, a debilitating and often fatal condition prevalent in South and Central America. With more than 20 million people infected the parasite poses a major health threat. The parasite uses sialic acid containing mucins to adhere to cells of the infected host, a prerequisite for cell invasion and parasite replication. However, T. cruzi is unable to synthesize the carbohydrate sialic acid de novo; instead it uses a trans-sialidase to scavenge this sugar from glycoconjugates of the infected host. Both the absence of trans-sialidase in mammals and its role in T. cruzi infectivity identify this enzyme as a potential target for therapeutic intervention. This project aims to determine the molecular detail of trans-sialidase substrate recognition and mechanism of action, which will provide new insights into the design and development of potential antibiotics. Our hypothesis is that a reductionism approach, employing model substrate analogues, is out of context and that we will only really learn how the enzyme works by analysing its interactions with the T. cruzi mucin glycopeptides that serve as substrates for the enzyme in vivo. It is not possible to obtain such materials in quantity, or in homogeneous form, from natural isolates.
The purpose of this project is to use a combination of state-of-the-art chemical and enzymatic synthesis to access homogeneous mucin glycopeptide fragments with which to probe specific issues about substrate recognition and turnover by trans-sialidase. This study serves to emphasise the key role for synthetic organic chemistry in post-genomic science, enabling structural biology and providing tools to delineate biological function. The project builds on the applicants expertise in synthetic and bioorganic chemistry, obtained during PhD studies with van Boom in Leiden (Netherlands), and applies it to an enzymology/chemical biology-led programme with Field in Norwich (UK).
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences chemical sciences organic chemistry
- natural sciences biological sciences biochemistry biomolecules carbohydrates
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs antibiotics
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
- natural sciences biological sciences molecular biology structural biology
You need to log in or register to use this function
Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP6-2002-MOBILITY-5
See other projects for this call
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
NORWICH
United Kingdom
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.