Investigation of a Novel Protein Implicated in Phosphate Metabolism in Bacteria. Phosphate is an important nutrient for all forms of life on Earth. A novel bacterial protein has been identified that appears to be important for the uptake or processing of phosphate, since mutants lacking the protein grow poorly inside certain cells of the human immune system (where phosphate levels are low) and in media containing low phosphate. The aims of this project are: to determine the role of the protein b ....Investigation of a Novel Protein Implicated in Phosphate Metabolism in Bacteria. Phosphate is an important nutrient for all forms of life on Earth. A novel bacterial protein has been identified that appears to be important for the uptake or processing of phosphate, since mutants lacking the protein grow poorly inside certain cells of the human immune system (where phosphate levels are low) and in media containing low phosphate. The aims of this project are: to determine the role of the protein by examining all phosphate containing molecules in our mutants; to determine its location in bacteria and functional domains; to identify other affected genes in our mutants; and, to find proteins that interact with this new protein. This project expects to demonstrate the importance of this protein in phosphate metabolism in bacteria.Read moreRead less
Using viral inhibitors to understand the regualtion of apoptosis. Apoptosis is a form of cell death that is critical for the development and well-being of multicellular organisms. The activity of Bak or Bax, two members of the Bcl-2 family, are essential for apoptosis to proceed, but how the activity of these two proteins is regulated is unclear. Many viruses encode inhibitors of apoptosis and the project will make use of two novel viral inhibitors that specifically target Bak. The project aims ....Using viral inhibitors to understand the regualtion of apoptosis. Apoptosis is a form of cell death that is critical for the development and well-being of multicellular organisms. The activity of Bak or Bax, two members of the Bcl-2 family, are essential for apoptosis to proceed, but how the activity of these two proteins is regulated is unclear. Many viruses encode inhibitors of apoptosis and the project will make use of two novel viral inhibitors that specifically target Bak. The project aims to determine how the Bak inhibitors function and to provide valuable insights into the normal mechanisms regulating Bak activity.Read moreRead less
Regulating nutrient uptake in intracellular parasites. Parasites impose a major economic and medical burden on human societies. In order to grow and reproduce, parasites scavenge nutrients from their animal or human hosts. As they move within and between hosts they encounter different levels of nutrients; how they adapt to these differences is poorly understood. This project aims to investigate the mechanisms by which the model parasite Toxoplasma senses and responds to the nutrients in its envi ....Regulating nutrient uptake in intracellular parasites. Parasites impose a major economic and medical burden on human societies. In order to grow and reproduce, parasites scavenge nutrients from their animal or human hosts. As they move within and between hosts they encounter different levels of nutrients; how they adapt to these differences is poorly understood. This project aims to investigate the mechanisms by which the model parasite Toxoplasma senses and responds to the nutrients in its environment, thereby shedding light on how they adapt to the different environments that they inhabit and, in the longer term, informing novel treatment strategies that aim to limit the parasites’ nutrient supply.Read moreRead less
Molecular basis of synergy between PIs and defensins against fungi. The plant defensin nicotinamide adenine dinucleotide dehydrogenase subunit 1 (NaD1) has potent antifungal activity against agricultural and human pathogens and has potential in the treatment of serious diseases that affect crop production and human health. NaD1 has been found to permeabilise membranes and allows entry of other molecules into the fungal cytoplasm. While screening for molecules that enhance the activity of defensi ....Molecular basis of synergy between PIs and defensins against fungi. The plant defensin nicotinamide adenine dinucleotide dehydrogenase subunit 1 (NaD1) has potent antifungal activity against agricultural and human pathogens and has potential in the treatment of serious diseases that affect crop production and human health. NaD1 has been found to permeabilise membranes and allows entry of other molecules into the fungal cytoplasm. While screening for molecules that enhance the activity of defensins a number of proteinase inhibitors were identified that act synergistically with NaD1. This project aims to identify the molecular basis of this synergy which is expected to lead to better control of fungal diseases of crops and in humans.Read moreRead less
Host-pathogen interactions: the role of mimicry. The proposed research program, using a combination of structure and functional analysis will provide insight into the mechanism of nucleotide hydrolysis by the enzymes NTPDases. This study will not only improve our fundamental understanding of NTPDase action but could lead to the rational design of antimicrobials.
A conserved pathway of cell death in response to invading DNA. This project aims to characterise molecular details of a new pathway of foreign DNA recognition and rapid cell death. Recognition of foreign DNA is a key means by which both bacteria and eukaryotic cells can detect infections, as well as guard their own genome. Eukaryotic cell DNA is sequestered in the nucleus and organelles, and any DNA found in the cytosol is a danger signal. The project proposes that cytosolic DNA-induced cell dea ....A conserved pathway of cell death in response to invading DNA. This project aims to characterise molecular details of a new pathway of foreign DNA recognition and rapid cell death. Recognition of foreign DNA is a key means by which both bacteria and eukaryotic cells can detect infections, as well as guard their own genome. Eukaryotic cell DNA is sequestered in the nucleus and organelles, and any DNA found in the cytosol is a danger signal. The project proposes that cytosolic DNA-induced cell death is a fundamental eukaryotic defensive response, but surprisingly, the known pathway is restricted to macrophages of some mammals. Project outcomes may be applied to protein expression yield in biotechnology or advances in gene therapy.Read moreRead less
Structural and functional analysis of the protein kinase R. We have shown that protein kinase R (PKR) plays a key role in regulating the body's response to virus infections, inflammation and cancer. This project will identify mechanisms that regulate the activity of PKR and provide information useful for the development of novel drugs.
New guardians of the mucosa: Molecular characterisation of M cell biology. We aim to completely define the cellular and molecular biology of gut and lung M cells for the first time. We will elucidate how they develop, are regulated and function at a molecular level, and how M cells maintain normal gut and lung tissues and induce immune responses to protect against microbial challenges. In the future, the new insights will be essential pre-requisites for the development of mucosal-based intervent ....New guardians of the mucosa: Molecular characterisation of M cell biology. We aim to completely define the cellular and molecular biology of gut and lung M cells for the first time. We will elucidate how they develop, are regulated and function at a molecular level, and how M cells maintain normal gut and lung tissues and induce immune responses to protect against microbial challenges. In the future, the new insights will be essential pre-requisites for the development of mucosal-based interventions and vaccines that protect the gut and lung from infectious and inflammatory issues. The harnessing of effective immune responses to control such challenges, are of enormous fundamental and long-standing biological interest, and are amongst the most important areas of current scientific research.Read moreRead less
Understanding how Plasmepsin V directs export of malaria virulence proteins to the host cell. This project aims to characterise how malaria parasites survive and manipulate infected host cells by exporting virulence proteins. This project may identify essential proteins that allow the malaria parasite to transform the host in order to survive, replicate and hide from the immune system and provide new data on protein export in liver-stages.
Unlocking malaria invasion by ultraresolution microscopy. This project describes the microscopic analysis of malaria-causing parasites invading human blood cells. The project aims to better understand how this invasion works and to understand how it might be inhibited.