Understanding how cells compact and segregate DNA in vertebrates. How a cell compacts and divides its DNA is still a major unanswered question in biology. This project will determine the way in which a cell compacts its DNA nearly ten thousand fold to allow the faithful and accurate segregation to daughter nuclei.
Quantum collision theory for astrophysics, fusion energy and hadron therapy. The project intends to investigate collision processes involving charged particles interacting with complex atoms and molecules. Although the theory of electron, positron and ion collisions with simple atoms and molecules has advanced in recent years, the corresponding computational modelling is difficult due to the mix of the countably and uncountably infinite spectrum of the target, the long-range Coulomb potential, a ....Quantum collision theory for astrophysics, fusion energy and hadron therapy. The project intends to investigate collision processes involving charged particles interacting with complex atoms and molecules. Although the theory of electron, positron and ion collisions with simple atoms and molecules has advanced in recent years, the corresponding computational modelling is difficult due to the mix of the countably and uncountably infinite spectrum of the target, the long-range Coulomb potential, and the multicentre nature of the target and the rearrangement processes. These difficulties could be overcome using a convergent close-coupling method. This project plans to apply the method to complex quantum collision systems in diverse applications of current interest such as fusion energy, lighting, astrophysics, and cancer imaging and therapy.Read moreRead less
Electrophile induced domino reaction sequences with ion-pair chiral induction. In this project, new catalysts and procedures will be developed to improve our capacity to access and modify the structure and properties of complex molecules. These methods will be used to gain access to a number of bioactive natural products in order to better evaluate and develop their therapeutic potential.
Nanoparticle formulations for DNA-targeted radiotherapy and imaging: combinations with chromatin-modifying compounds. This project will develop a new approach for treating and imaging cancer using nanoparticles which target specific cells for cancer therapy and diagnostic imaging. The nanoparticles will be combined with compounds that alter the architecture of DNA to make therapy more effective and to improve the safety of imaging.
The critical role of the class III histone deacetylase SIRT2 in stabilizing N-Myc oncoprotein. Cancer is the commonest cause of death from disease in children. Neuroblastoma is the commonest solid tumor in early childhood. This project will investigate the critical roles of SIRT2 protein in increasing the expression of N-Myc oncoprotein and consequently inducing neuroblastoma, and SIRT2 inhibitors as anticancer agents.
Mitochondrially targeted anti-cancer drugs modulate the mitochondrial genome. Successful cancer management requires novel therapeutical approaches. This project will test the effect of a new class of compounds that target mitochondria, the powerhouse of the cells, where they suppress expression of mitochondrial genes. By this mechanism, cancers that are resistant to apoptosis induction can be inhibited.
A new Src, PKCdelta and Akt regulated protease activated receptor system in metastasis. In contrast with localised cancer which can often be cured, curative treatment is generally not possible for cancer that has spread. This project will characterise a protein that drives the spread of cancer and to develop new approaches to treat patients at risk of developing these aggressive tumours that spread to other organs.
Molecular hallmarks of androgen receptor targeting in prostate cancer. There is a critical need in oncology drug development for better biomarkers of response to prostate cancer therapies, clinically to assist with treatment decision making, and pre-clinically to facilitate translation of emerging agents into clinical practice. Using a unique explant culture model, this project will identify protein and lipid markers that can be used to accurately and reliably assess response to androgen recepto ....Molecular hallmarks of androgen receptor targeting in prostate cancer. There is a critical need in oncology drug development for better biomarkers of response to prostate cancer therapies, clinically to assist with treatment decision making, and pre-clinically to facilitate translation of emerging agents into clinical practice. Using a unique explant culture model, this project will identify protein and lipid markers that can be used to accurately and reliably assess response to androgen receptor (AR)-targeting therapies in human prostate tumours. The identification and functional assessment of these biomarkers will identify those that can be used as surrogate endpoints in clinical trials, facilitate earlier approval of investigational agents and lead to improved options for therapeutic management of prostate cancer.Read moreRead less
Development of disulphide-rich peptides for drug design. Peptides are an outstanding source of potential drug leads. This project seeks to build on earlier breakthroughs by developing stable, peptide-based drugs to combat cancer and autoimmune diseases. The peptides, derived from natural sources, are anticipated to provide drug leads that can ultimately lead to treatments for these diseases.
Chromatin structure and pervasive transcription. This project aims to understand mechanisms that repress pervasive transcription and to identify chromatin characteristics that repress transcription initiation outside the promoter regions. Chromatin characteristics, such as position, occupancy and turnover-rate of nucleosomes, establish an elaborate genomic indexing mechanism, which defines functional units in the genome. Defects in this process increase pervasive transcription, toxic accumulatio ....Chromatin structure and pervasive transcription. This project aims to understand mechanisms that repress pervasive transcription and to identify chromatin characteristics that repress transcription initiation outside the promoter regions. Chromatin characteristics, such as position, occupancy and turnover-rate of nucleosomes, establish an elaborate genomic indexing mechanism, which defines functional units in the genome. Defects in this process increase pervasive transcription, toxic accumulation of non-coding transcripts and genomic instability. This work aims to understand eukaryotic genome organisation and may have long-term therapeutic implications for cancer and ageing-related diseases.Read moreRead less