Molecular Mechanisms of NOD signalling. Alterations in NOD1 and NOD2 (nucleotide-binding oligomerization domain containing 1 and 2) signalling have been implicated in various human inflammatory diseases. Therefore, a clear understanding of the molecular signalling pathways is important to gain further insights into potential drug targets for the treatment of these diseases. Using novel experimental approaches, this project aims to identify new members of the NOD signalling pathway. It will test ....Molecular Mechanisms of NOD signalling. Alterations in NOD1 and NOD2 (nucleotide-binding oligomerization domain containing 1 and 2) signalling have been implicated in various human inflammatory diseases. Therefore, a clear understanding of the molecular signalling pathways is important to gain further insights into potential drug targets for the treatment of these diseases. Using novel experimental approaches, this project aims to identify new members of the NOD signalling pathway. It will test the effect of pharmacological inhibition of established molecules such as RIPK2 or IAPs in NOD dependent models for human diseases. Outcomes of this study will be of the utmost interest for the treatment of NOD driven diseases such as Crohn's disease, Blau syndrome or asthma.Read moreRead less
Understanding T cell immunity induced by infection. We aim to understand how killer T cells are “programmed” upon activation and acquire their characteristic functions and how these are maintained into immunological memory. This proposal will provide insights important for the design and improvement of vaccine strategies to fight pathogens such as influenza, HIV and even tumors.
Investigating the actions of anti-inflammatory pathways in chronic lung disease. There is an urgent need to develop better drugs for Chronic Obstructive Pulmonary Disease (COPD) as patients become resistant to currently used anti-inflammatory drugs with disease progression. This research will uncover fundamental biology into an important class of anti-inflammatory receptor termed ALX/FPR2. This receptor normally coordinates the clearance of infection and injured tissue and subsequently switches ....Investigating the actions of anti-inflammatory pathways in chronic lung disease. There is an urgent need to develop better drugs for Chronic Obstructive Pulmonary Disease (COPD) as patients become resistant to currently used anti-inflammatory drugs with disease progression. This research will uncover fundamental biology into an important class of anti-inflammatory receptor termed ALX/FPR2. This receptor normally coordinates the clearance of infection and injured tissue and subsequently switches off inflammation. Essential knowledge into why this receptor pathway fails to switch off inflammation will be determined. Furthermore, the development of targeting strategies to this receptor represents an innovative approach to blocking damaging and chronic airway inflammation.Read moreRead less
Developmental programming of adult stress responses: early life nutrition permanently alters stress and immune function. Obese children are more likely to grow up to be obese adults than normal-weight children are. Their early life diet may be at least partly to blame. Early life nutrition can also compromise ability to respond to stress or inflammation. This project will investigate how this occurs and if these effects are specific to the developmental period.
Understanding endogenous allosteric modulators of G protein-coupled receptors. Major life science challenges include how chemicals outside cells signal to proteins inside, how this results in physiological responses, and how dysfunction of these processes leads to pathophysiology. Despite the critical importance of G protein-coupled receptors (GPCRs), much remains to be learned about their regulation by endogenous and synthetic molecules. This project aims to address this gap, by building on rec ....Understanding endogenous allosteric modulators of G protein-coupled receptors. Major life science challenges include how chemicals outside cells signal to proteins inside, how this results in physiological responses, and how dysfunction of these processes leads to pathophysiology. Despite the critical importance of G protein-coupled receptors (GPCRs), much remains to be learned about their regulation by endogenous and synthetic molecules. This project aims to address this gap, by building on recent ground-breaking studies that have been performed, by focusing on alternative binding sites of GPCRs called allosteric sites. The major hypothesis is that these allosteric sites are widespread across GPCRs because the body produces endogenous allosteric ligands that remain largely unidentified, but which can play vital roles in biology.Read moreRead less
Crosstalk between breast cancer cells and the microenvironment to promote metastasis. Breast cancer spread (metastasis) to distant tissues is usually fatal. It is now clear that cross-talk between cancer cells and other normal cells is essential for metastasis and previous studies have discovered two key mechanisms: tumour cell suppression of immune defence pathways to escape immune recognition, and activation of proteases to promote invasion and blood vessel growth. Using unique models and cell ....Crosstalk between breast cancer cells and the microenvironment to promote metastasis. Breast cancer spread (metastasis) to distant tissues is usually fatal. It is now clear that cross-talk between cancer cells and other normal cells is essential for metastasis and previous studies have discovered two key mechanisms: tumour cell suppression of immune defence pathways to escape immune recognition, and activation of proteases to promote invasion and blood vessel growth. Using unique models and cellular imaging, this project aims to investigate the cell specific functions of these pathways and the therapeutic potential of altering their expression and function. This project may lead to the development of novel predictors of metastasis in patients and new targeted therapeutics to prevent breast cancer spread.Read moreRead less
Transcriptional and epigenetic regulation of terminal lymphocyte differentiation and alterations of the same that lead to leukemia. In the developed world infection diseases are the number three killer behind heart disease and cancer, and huge financial effort is put into treatment and prevention. Despite this, results have often been disappointing. One cause of these poor outcomes is the lack of knowledge of how effective immune responses are generated. This project aims to better understand th ....Transcriptional and epigenetic regulation of terminal lymphocyte differentiation and alterations of the same that lead to leukemia. In the developed world infection diseases are the number three killer behind heart disease and cancer, and huge financial effort is put into treatment and prevention. Despite this, results have often been disappointing. One cause of these poor outcomes is the lack of knowledge of how effective immune responses are generated. This project aims to better understand the processes that control the generation of protective lymphocytes. It will deliver information that may enable a more targeted approach to vaccine-development and treatments of infections. As defective differentiation can also be a cause of leukemia it may also lead to targets of cancer treatment.Read moreRead less
Controlling apoptotic cell death in health and disease. Regulating how and when cells die is crucial for the development and maintenance of a healthy body and mind. This project will investigate the proteins that are responsible for controlling cell death with the view to identifying novel ways to target these proteins for the treatment of disorders such as cancer, neurodegenerative disease and autoimmunity.
Imaging the generation and recall of protective antiviral immune responses in vivo. Our understanding of the in vivo dynamics of cellular immune responses to infectious diseases is poor. This project will utilise advanced intravital imaging combined with novel tools to dissect the cellular events involved in the generation and recall of T cell responses to localised virus infection, combined with a detailed functional analysis of the lymphoid organ stroma. Such fundamental information will contr ....Imaging the generation and recall of protective antiviral immune responses in vivo. Our understanding of the in vivo dynamics of cellular immune responses to infectious diseases is poor. This project will utilise advanced intravital imaging combined with novel tools to dissect the cellular events involved in the generation and recall of T cell responses to localised virus infection, combined with a detailed functional analysis of the lymphoid organ stroma. Such fundamental information will contribute to the development of new generation vaccines and therapies to protect against tissue-specific infectious diseases, cancers and autoimmune diseases.Read moreRead less
The regulation of anti-viral immunity by host and viral proteins. Anti-viral immunity is initially triggered when specific immune sensors detect viral components within the cell. This project will use a combined functional/structural approach to investigate the specifics of immune activation by a pivotal immune sensor and use this information to understand how influenza A sabotages this specific immune response.