The Role Of UPF3B And Nonsense Mediated MRNA Decay Surveillance In The Pathology Of Intellectual Disability.
Funder
National Health and Medical Research Council
Funding Amount
$789,954.00
Summary
Proper functioning of the nonsense mediated mRNA decay (NMD or 'mRNA police') is crucial for any cell to ensure normal development and function. When NMD is compromised the outcome is learning and memory problems, autism or schizophrenia. Under this project we study malfunctioning NMD using stem and neuronal cells derived from patients' skin cells. Some of the affected genes might be considered for therapeutic interventions. NMD is relevant to 1000s of human disorders and as such it is of fundam ....Proper functioning of the nonsense mediated mRNA decay (NMD or 'mRNA police') is crucial for any cell to ensure normal development and function. When NMD is compromised the outcome is learning and memory problems, autism or schizophrenia. Under this project we study malfunctioning NMD using stem and neuronal cells derived from patients' skin cells. Some of the affected genes might be considered for therapeutic interventions. NMD is relevant to 1000s of human disorders and as such it is of fundamental importance.Read moreRead less
Integrating Immunity And Genetics In Follicular Lymphoma To Establish A Prognostic Score Fit For The Modern Era
Funder
National Health and Medical Research Council
Funding Amount
$1,377,174.00
Summary
Follicular lymphoma (FL) is divided into early and advanced stages. Early stage FL is frequently cured, but there is no way to identify who will be cured and who won't. By contrast advanced stage FL is incurable. Our unique access to well-annotated clinical trial and population based cohorts allows us to perform a detailed biological comparison of early and advanced FL, to gain a deeper understanding of the impediments to eradicating the disease, and to predict outcome to conventional therapy.
Differential Regulation Of Endometrial Gene Expression In Endometriosis And Disease Subtypes
Funder
National Health and Medical Research Council
Funding Amount
$163,276.00
Summary
The endometrium or tissue lining the inside of the uterus is important in implantation and pregnancy, and is implicated in diseases including endometriosis. This project aims to use RNA sequencing to provide a detailed picture of gene expression in the endometrium and combine these results with our existing data to examine genetic control of gene regulation around the time of implantation and in regions of the genome associated with endometriosis and other diseases.
Transcription Factors Which Regulate Signalling Through The Leptin-Melanocortin Pathway
Funder
National Health and Medical Research Council
Funding Amount
$586,704.00
Summary
Specific gene regulatory proteins define functions of various subsets of neurons in the hypothalamus. We will determine how interactions between three such proteins activate the leptin-melanocortin pathway, a hypothalamic signalling circuit that controls appetite. Defects in these proteins are found in obese patients who suffer from excessive eating disorders. The project will improve understanding of the genetic determinants of obesity and provide key points for development of new therapies.
Uncovering New Epigenetic-based Regulatory Mechanisms Of Gene Expression: Novel Links Between Histone Variants, RNA Function And Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,053,671.00
Summary
It is estimated that greater than 90% of human genes undergo alternative RNA splicing, which can explain how protein diversity is achieved with a limited number of genes. However, how alternative splicing patterns are established remains poorly understood but is an important question given that 15-50% of human disease mutations are associated with changes to the splicing patterns of RNA. We have uncovered a new splicing mechanism, which involves changing the way DNA is packaged in a cell.
Molecular Control Of Interneuron Development And Function In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$527,828.00
Summary
This project will study the changes that occur in neurons, during normal brain maturation and in pathology. We hypothesise that early signs of brain malfunction can be detected in neurons before symptoms appear. The role of a gene will be studied during development and disease in a mouse model of autism, in order to identify the molecular and electrical signs of abnormal activity. This research will ultimately enable us to propose new strategies to treat symptoms of brain disease.
Regulating Gene Expression Changes In Cardiac Hypertrophy
Funder
National Health and Medical Research Council
Funding Amount
$690,754.00
Summary
Following the success in decoding human genome, i.e. DNA sequence, a major task is to understand how the activity of genes with consequent changes in respective proteins. As proteins are an important component for cell structure and function, such changes in quantity and quality of proteins will play a pivotal role to affect disease development and progression.
Clinical Classification Of Regulatory Variants In Breast Cancer Susceptibility Genes
Funder
National Health and Medical Research Council
Funding Amount
$536,966.00
Summary
Variations in our genes can confer a risk of diseases including breast cancer. Determining the clinical significance of these variations is a major and increasing challenge for genetic counselors and clinicians. This project will evaluate the clinical significance of variants in the control regions of breast cancer susceptibility genes. This research will inform the development of guidelines for interpreting such variants in a clinical setting.
Genomic Analysis Of The Novel Epigenetic Modifier Smchd1 As A Tumour Suppressor
Funder
National Health and Medical Research Council
Funding Amount
$619,142.00
Summary
Epigenetic modifications are changes made to our DNA that act like punctuation marks in the genome, to instruct the cell when to turn genes on and when to switch them off. Epigenetic control is critical to range of different biological processes, and also goes awry in cancer. We are specifically interested in the role of one new protein involved in epigentic control and characterising its role as a tumour suppressor.
Identifying Cell Type Specific Biomarkers Of Recurrent Oral Squamous Cell Carcinoma And Mapping Cancer-stroma Interactions Using Single Cell Biology And Cell-to-cell Communication Networks
Funder
National Health and Medical Research Council
Funding Amount
$892,858.00
Summary
Cancer is a major cause of death in Australia. Despite advances in our understanding of the mutations that occur and the sets of genes expressed in cancer we have a major gap in our understanding of what is happening within tumours. Using new single cell technology we will generate new molecular portraits of cancers that give us understanding of the sets of genes expressed on individual cancer cells, the normal cells within a tumour and how they interact with cancer cells to form a tumour.