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
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
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.
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