Molecular Basis of Sugar Transport in Mycobacterium tuberculosis
Lead Research Organisation:
University of Warwick
Department Name: Warwick Medical School
Abstract
Programme overview:
This MRC-funded doctoral training partnership (DTP) brings together cutting-edge molecular and analytical sciences with innovative computational approaches in data analysis to enable students to address hypothesis-led biomedical research questions. This is a 4-year programme whose first year involves a series of taught modules and two laboratory-based research projects that lead to an MSc in Interdisciplinary Biomedical Research. The first two terms consist of a selection of taught modules that allow students to gain a solid grounding in multidisciplinary science. Students also attend a series of masterclasses led by academic and industry experts in areas of molecular, cellular and tissue dynamics, microbiology and infection, applied biomedical technologies and artificial intelligence and data science. During the third and summer terms students conduct two eleven-week research projects in labs of their choice.
Project overview:
Tuberculosis (TB), caused by Mycobacterium tuberculosis, claims the lives of millions of people each year globally, but the current treatment is long and not always effecEve. Resistance levels are increasing and there is a growing need for new treatments. Therefore, we urgently need to understand the basic biology of this global pathogen to aid its eradicaEon. Mtb is unusual as it survives in humans for decades but it is not known which nutrients are criEcal or indeed how they are transported into the bacteria. From interrogaEon of the genome Mtb is predicted to have five putaEve carbohydrate transporters, and the precise funcEon and physiology role of these import systems needs to be determined. This interdisciplinary proposal will aim to study all five of these transport systems and combine experimental techniques with computaEonal modelling to provide new insights into these Mtb transporters, which would be unavailable any other way.
ComparaEve modelling will be used to characterise carbohydrate transport in Mtb based on available crystal structures, and ligand docking will help guide potenEal substrate candidates that are transported by these processes. Using the crystal structures and homology models, molecular dynamic (MD) simulaEons will be performed. There will be mulEple aims for MD simulaEons: increase our understanding of the mechanism of transport, idenEfy key residues, ascertain key contacts between the ligand and protein and study effects of mutants on transport. This informaEon will then be used to inform the design of potenEal inhibitors and test these compounds experimentally. QuanEtaEve Skills in soXware for docking, MD simulaEons and homology modelling will be obtained, along with programming in python for analysis of this. Alongside experimental techniques will be developed to validate the results such as protein-ligand binding studies and X-ray crystallography.
This MRC-funded doctoral training partnership (DTP) brings together cutting-edge molecular and analytical sciences with innovative computational approaches in data analysis to enable students to address hypothesis-led biomedical research questions. This is a 4-year programme whose first year involves a series of taught modules and two laboratory-based research projects that lead to an MSc in Interdisciplinary Biomedical Research. The first two terms consist of a selection of taught modules that allow students to gain a solid grounding in multidisciplinary science. Students also attend a series of masterclasses led by academic and industry experts in areas of molecular, cellular and tissue dynamics, microbiology and infection, applied biomedical technologies and artificial intelligence and data science. During the third and summer terms students conduct two eleven-week research projects in labs of their choice.
Project overview:
Tuberculosis (TB), caused by Mycobacterium tuberculosis, claims the lives of millions of people each year globally, but the current treatment is long and not always effecEve. Resistance levels are increasing and there is a growing need for new treatments. Therefore, we urgently need to understand the basic biology of this global pathogen to aid its eradicaEon. Mtb is unusual as it survives in humans for decades but it is not known which nutrients are criEcal or indeed how they are transported into the bacteria. From interrogaEon of the genome Mtb is predicted to have five putaEve carbohydrate transporters, and the precise funcEon and physiology role of these import systems needs to be determined. This interdisciplinary proposal will aim to study all five of these transport systems and combine experimental techniques with computaEonal modelling to provide new insights into these Mtb transporters, which would be unavailable any other way.
ComparaEve modelling will be used to characterise carbohydrate transport in Mtb based on available crystal structures, and ligand docking will help guide potenEal substrate candidates that are transported by these processes. Using the crystal structures and homology models, molecular dynamic (MD) simulaEons will be performed. There will be mulEple aims for MD simulaEons: increase our understanding of the mechanism of transport, idenEfy key residues, ascertain key contacts between the ligand and protein and study effects of mutants on transport. This informaEon will then be used to inform the design of potenEal inhibitors and test these compounds experimentally. QuanEtaEve Skills in soXware for docking, MD simulaEons and homology modelling will be obtained, along with programming in python for analysis of this. Alongside experimental techniques will be developed to validate the results such as protein-ligand binding studies and X-ray crystallography.
Organisations
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| MR/N014294/1 | 01/10/2016 | 30/09/2025 | |||
| 2269666 | Studentship | MR/N014294/1 | 01/10/2019 | 30/09/2023 |