A molecular investigation into the naïve T cell repertoire. This project aims to interrogate the relationship between T cell receptor (TCR) recognition modes and T cell recruitment and activation. CD8+ T cells are important for adaptive immunity. Their recognition, via TCR, of peptides bound to MHC class I antigen-presenting molecules (pMHCI), initiates a signalling cascade which activates T cells effector functions. All structural information on TCR recognition of pMHCI is based on TCRs prevale ....A molecular investigation into the naïve T cell repertoire. This project aims to interrogate the relationship between T cell receptor (TCR) recognition modes and T cell recruitment and activation. CD8+ T cells are important for adaptive immunity. Their recognition, via TCR, of peptides bound to MHC class I antigen-presenting molecules (pMHCI), initiates a signalling cascade which activates T cells effector functions. All structural information on TCR recognition of pMHCI is based on TCRs prevalent in immune responses, and all recognise pMHCI using a conserved orientation. This project aims to use this observation to study the relationship between TCR recognition modes and T cell recruitment and activation.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.
Programmed cell death in host-microbe interactions. This project aims to address how host cell death, as part of the immune defence system, controls invading microbes. By following host-microbe interactions at high resolution, the project will generate new knowledge in the area of infection and immunity based on an interdisciplinary approach to discover new cell death factors. The expected outcome of this project will enhance the imaging capacity and develop new technologies in Australia by buil ....Programmed cell death in host-microbe interactions. This project aims to address how host cell death, as part of the immune defence system, controls invading microbes. By following host-microbe interactions at high resolution, the project will generate new knowledge in the area of infection and immunity based on an interdisciplinary approach to discover new cell death factors. The expected outcome of this project will enhance the imaging capacity and develop new technologies in Australia by building on international collaborations, providing significant benefits to the health of the community and potential to develop innovative applications in biomedical industries.Read moreRead less
Investigating the molecular basis of T-cell receptor cross-reactivity. This project will explore the basis of unexpected immune reactions whereby the immune system mistakes one molecular structure for another, a phenomenon known as cross-reactivity. This project will examine how often this is due to molecular mimicry, potentially explaining why immune T cells sometimes react inappropriately to different agents.
Molecular mechanisms of cyclic Adenosine Monophosphate (AMP) induced apoptosis. Cyclic Adenosine Monophosphate (cAMP) is an important cellular chemical necessary for cell growth. However, de-regulated cAMP production in response to altered physiology can result in cellular death or apoptosis. This is attributed to the development of certain human diseases and this project aims to understand the molecular mechanism behind this process.
Moonlighting from sugar to metal. This project intends to use integrated genetics, biochemistry and omics to decipher the roles of the highly conserved OST3 proteins, which have been implicated in the disparate functions of regulating protein glycosylation and transporting magnesium. The project plans to detail the role of OST3 proteins in regulating mammalian glycosylation and reconstruct the vertebrate co-evolutionary trajectory of OST3 protein–substrate interactions. It also aims to identify ....Moonlighting from sugar to metal. This project intends to use integrated genetics, biochemistry and omics to decipher the roles of the highly conserved OST3 proteins, which have been implicated in the disparate functions of regulating protein glycosylation and transporting magnesium. The project plans to detail the role of OST3 proteins in regulating mammalian glycosylation and reconstruct the vertebrate co-evolutionary trajectory of OST3 protein–substrate interactions. It also aims to identify and characterise the regulation, mechanisms and metabolic consequences of OST3 protein-mediated magnesium transport. These outcomes may provide insights into eukaryotic biology, and allow advances in engineered systems for glycoprotein production and modulating cellular metabolism with potential research and therapeutic utility.Read moreRead less
Membrane proteins in innate immunity. The application of smarter and faster methods for understanding membrane proteins, targets of most drugs, is vital to a knowledge-based economy and a healthy society. The long-term benefits will include fundamental new knowledge on immunity, and implementation of new approaches that streamline costs and efforts of challenging, high-impact research.
Structure and function of human zinc transporter membrane proteins. The aim of this project is to create fundamental new knowledge on how important mammalian membrane proteins operate. Membrane proteins are key drug targets and are significantly under-represented in structural databases. The project plans to combine innovative membrane protein screening technology with gene expression, structural biology, biophysics and cell biology. The project outcomes may elucidate specific molecular mechanis ....Structure and function of human zinc transporter membrane proteins. The aim of this project is to create fundamental new knowledge on how important mammalian membrane proteins operate. Membrane proteins are key drug targets and are significantly under-represented in structural databases. The project plans to combine innovative membrane protein screening technology with gene expression, structural biology, biophysics and cell biology. The project outcomes may elucidate specific molecular mechanisms underpinning the essential biological process of zinc homeostasis.Read moreRead less
Investigating the structure of a T cell immune checkpoint molecule. This project aims to investigate the basic structure and function of a key co-receptor expressed on T cells, known as lymphocyte activation gene-3. T cells play a role in the immune system but must be managed to prevent autoimmunity. Insight into the function of the lymphocyte activation gene-3 function can be used to tailor immunotherapeutics to treat a variety of diseases, including cancer. Functionality of the T cell recept ....Investigating the structure of a T cell immune checkpoint molecule. This project aims to investigate the basic structure and function of a key co-receptor expressed on T cells, known as lymphocyte activation gene-3. T cells play a role in the immune system but must be managed to prevent autoimmunity. Insight into the function of the lymphocyte activation gene-3 function can be used to tailor immunotherapeutics to treat a variety of diseases, including cancer. Functionality of the T cell receptor is determined by utilising structural biology and cellular immunology techniques. The impact of this project effects the development of innovative T cell immunomodulatory agents, improving the health and quality of life of the Australian population.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE160100097
Funder
Australian Research Council
Funding Amount
$675,000.00
Summary
An Automated Protein Nano-Crystallisation Facility. An automated protein nano-crystallisation facility:
The project aims to establish a high throughput protein nanocrystallisation and imaging facility for protein crystallography. Protein crystallography is an important field of biological research, however there are many proteins, such as integral membrane proteins and transient molecular complexes that are more challenging to crystallise. The facility aims to use state-of-the-art imaging and c ....An Automated Protein Nano-Crystallisation Facility. An automated protein nano-crystallisation facility:
The project aims to establish a high throughput protein nanocrystallisation and imaging facility for protein crystallography. Protein crystallography is an important field of biological research, however there are many proteins, such as integral membrane proteins and transient molecular complexes that are more challenging to crystallise. The facility aims to use state-of-the-art imaging and crystallisation techniques, including second order nonlinear imaging of chiral crystals (SONICC) imaging and lipid cubic phase approaches, to enable structural studies to be undertaken on challenging proteins. This information is often used for the rational development of therapeutics. The facility would support cutting-edge biological research In Australia.Read moreRead less