Solving the puzzle of complex disease - genes and their interactions with the environment. Many human diseases are caused by the interplay of genetic predisposition (nature) and the environment (nurture); but their causes remain a mystery, since much past research has focused on these aspects in isolation. This project will aim to better understand these complex diseases using a multi-factorial approach that brings both nature and nurture together.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE110100092
Funder
Australian Research Council
Funding Amount
$300,000.00
Summary
Fluorescence microscopy with optical tweezers: imaging cellular responses. Life relies on the ability of our cells to receive and respond to signals with pinpoint accuracy, involving both chemical and mechanical signals. This equipment will allow scientists to expose cells to both types of signals and measure the response at an unprecedented level of accuracy for the first time.
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
Predicting adaptation and range expansion under climate change. This project investigates the repeatability and thereby the predictability of adaptation to climate change by leveraging 1000 genomes sampled over 150 years and multiple climatic gradients in the rapidly adapting, globally invasive, and highly allergenic ragweed. We expect to deepen our understanding of the genetic basis of adaptation and decipher the circumstances under which adaptive genetic change is repeatable, by integrating a ....Predicting adaptation and range expansion under climate change. This project investigates the repeatability and thereby the predictability of adaptation to climate change by leveraging 1000 genomes sampled over 150 years and multiple climatic gradients in the rapidly adapting, globally invasive, and highly allergenic ragweed. We expect to deepen our understanding of the genetic basis of adaptation and decipher the circumstances under which adaptive genetic change is repeatable, by integrating a novel evolutionary model with genomic data. We will develop the capacity to predict species’ distributions and trait evolution under climate change using a powerful empirical dataset. This will provide us with the capacity to anticipate and manage the effects of climate change on noxious and threatened species.Read moreRead less
The epigenetic blueprint for T cell differentiation: a genomic view. A cardinal feature of adaptive immune cell activation is the initiation of a program of differentiation that results in acquisition and long term maintenance of lineage-speci?c effector function. This proposal aims to map and dissect genome wide molecular changes that occur at different stages of immune cell differentiation and identify key factors that regulating these changes. It is expected that distinct genomic signatures, ....The epigenetic blueprint for T cell differentiation: a genomic view. A cardinal feature of adaptive immune cell activation is the initiation of a program of differentiation that results in acquisition and long term maintenance of lineage-speci?c effector function. This proposal aims to map and dissect genome wide molecular changes that occur at different stages of immune cell differentiation and identify key factors that regulating these changes. It is expected that distinct genomic signatures, and the mechanisms indicative of effective immune cell differentiation will be identified. This proposal will provide insights into key mechanisms that result in reprogramming of immune cell function and memory and have implications for understanding general cellular differentiation.Read moreRead less
Differentiation of effector and tissue regulatory T cells . Regulatory T cells (Tregs) populate almost every organ of the body and play a central role in preventing inflammation and maintaining health. To exercise these functions, Tregs undergo a developmental program, the details of which are poorly known. This project will utilize newly developed biological tools and state-of-the-art technology to uncover the molecular mechanisms that govern Treg development and function. The project will gene ....Differentiation of effector and tissue regulatory T cells . Regulatory T cells (Tregs) populate almost every organ of the body and play a central role in preventing inflammation and maintaining health. To exercise these functions, Tregs undergo a developmental program, the details of which are poorly known. This project will utilize newly developed biological tools and state-of-the-art technology to uncover the molecular mechanisms that govern Treg development and function. The project will generate basic scientific knowledge and new intellectual property that will afford new opportunities for research and development. The outcomes of this project will help to devise strategies to treat diseases such as autoimmunity, cancer and metabolic syndrome, and will thus benefit veterinary and human health.Read moreRead less
How enhancers regulate T cell differentiation and function. This project aims to identify the molecular mechanisms that regulate the activity of transcriptional enhancers needed for effective immune cell differentiation. Adaptive immune cell activation starts a programme of differentiation that acquires and maintains lineage-specific effector function. Using a multidisciplinary approach including cellular and chromatin biology, advanced bioinformatics, targeted genome editing and nanotechnology, ....How enhancers regulate T cell differentiation and function. This project aims to identify the molecular mechanisms that regulate the activity of transcriptional enhancers needed for effective immune cell differentiation. Adaptive immune cell activation starts a programme of differentiation that acquires and maintains lineage-specific effector function. Using a multidisciplinary approach including cellular and chromatin biology, advanced bioinformatics, targeted genome editing and nanotechnology, this project expects to provide insights into non-coding regulatory element reprogramming and control of immune cell function and memory with implications for understanding general cellular differentiation.Read moreRead less
The T cell genome in 3D: linking chromatin structure to cellular function. Adaptive immune cell activation results in the acquisition and long term maintenance of specific cellular function that enables efficient immune control of infections. Using advanced cellular and genomic approaches, combined with high-resolution microscopy and cutting edge computational biology, this proposal aims to address major gaps in our knowledge about how alterations in genomic 3D architecture and targeted biochemi ....The T cell genome in 3D: linking chromatin structure to cellular function. Adaptive immune cell activation results in the acquisition and long term maintenance of specific cellular function that enables efficient immune control of infections. Using advanced cellular and genomic approaches, combined with high-resolution microscopy and cutting edge computational biology, this proposal aims to address major gaps in our knowledge about how alterations in genomic 3D architecture and targeted biochemical modifications impact cell specific gene nuclear positioning and how this regulates changes in gene expression associated with immune cell activation. An outcome will be identification of novel molecular mechanisms that will have broad applicability across cellular biology, and provide novel targets for drug development.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE110100106
Funder
Australian Research Council
Funding Amount
$350,000.00
Summary
An advanced flow cytometry facility for the Peter Doherty Institute. The establishment of a flow cytometry facility in the new Peter Doherty Institute for Infection and Immunity will enhance capacity to investigate immunity to a broad range of very serious diseases. This project will support researchers studying viral and bacterial infection as well as cancer and autoimmunity.
microRNAs and the control of T lymphocyte differentiation, function and malignant transformation. The molecular mechanism of the immune system is not completely understood. This project will investigate how transcription factors and microRNAs, two major types of regulatory molecules work together to control immune responses. The results from this research will assist in the design of better vaccination strategies and treat certain lymphomas.