Projects: MESI-STRAT, Systems modelling age-related changes in the maintenance of dermal extra-cellular matrix: mechanisms and interventions, Are microRNAs key mediators of cartilage destruction in osteoarthritis?, Dynamic interplay between nuclei and mitochondria in ageing cells
Institutions: University of Newcastleorcid.org/0000-0003-3096-6386
I am a postdoc in the lab of Rick Lewis working on the biophysical characterization of protein-protein complexes involved in central carbon metabolism.
The main component of research in my group is in the determination of macromolecular structures by X-ray crystallography. However, since not all proteins crystallize, every effort is made to complete our understanding of how proteins function by utilizing other methods, such as microbial genetics, monitoring protein:ligand interactions by biochemical and biophysical methods, electron microscopy and bioinformatics
Tools: molecular biological techniques (RNA/DNA techniques), protein interaction studies, DNA technology RNA technology Protein analysis Fermentation Mutagenesis, gene regulation, Proteomics (2D-PAGE), Model organisms, Proteomics, Transcriptomics, Genetic analysis, Genomics, Cell biology, Biochemistry and protein analysis, Molecular Biology, Microbiology
Optimisation of Bacillus subtilis for the secretion of heterologous proteins Therapeutic proteins (including those required for experimental purposes and clinical trials) are major products of biomanufacturing processes and considerable time and expense are expended to maximise the yield and quality of proteins produced in heterologous hosts. The production host of choice is the Gram-negative bacterium Escherichia coli for which many strains and expression systems have been developed. However,
We will systematically analyse large datasets of multiple types to: (i) identify key components
affected by age or experimental perturbation; (ii) establish networks of interaction; (iii) develop dynamic
computational models based on these networks; (iv) use model selection methods to discriminate between
alternative network topologies and generate predictive models. To characterise the data, we will apply an
ensemble of methods, including frameworks in R/Bioconductor and toolboxes connected via
Public web page: Not specified
Organisms: Not specified
MESI-STRAT: Systems Medicine of Metabolic-Signaling Networks -A New Concept for Breast Cancer Patient Stratification.
Breast cancer is a complex disease with high prevalence in the European Union and world-wide. 75%-80 of the patients have estrogen receptor-positive (ER)-positive tumors and are treated with endocrine therapies. Endocrine therapies, which block ER-driven tumor growth, show high efficacy. Yet, a significant proportion of the patients will eventually relapse with metastatic breast
Overall, we will measure in-vitro and model in-silico the short-term biochemical network dynamics of extra cellular matrix maintenance (ECM) in populations of young, old and senescent dermal fibroblasts. We have shown in previous work that differences in network dynamics are highly informative and provide a means to identify parts of the network that could be targeted to restore healthy function.
The work will be first carried out in 2D culture of human dermal fibroblasts then extended to a novel
Organisms: Not specified
MicroRNAs are a recently discovered group of factors that control cell behaviour. There are thousands of microRNAs, but specific ones control the behaviour of cartilage cells and have key roles in osteoarthritis. Changing the level of a single microRNA can alter osteoarthritis, but we know that several microRNAs change during disease. The group has identified four microRNAs which have key roles in cartilage. This programme seeks:
to show that these microRNAs have a role in osteoarthritis in the
Public web page: http://dunhillmedical.org.uk/project/david-young-programme/
Organisms: Not specified
Systems Biology studies the properties and phenotypes that emerge from the interaction of biomolecules where such properties are not obvious from those of the individual molecules. By connecting fields such as genomics, proteomics, bioinformatics, mathematics, cell biology, genetics, mathematics, engineering and computer sciences, Systems Biology enables discovery of yet unknown principles underlying the functioning of living cells. At the same time, testable and predictive models of complex
Modelling carbon core metabolism in Bacillus subtilis – Exploring the contribution of protein complexes in core carbon and nitrogen metabolism.
Bacillus subtilis is a prime model organism for systems biology approaches because it is one of the most advanced models for functional genomics. Furthermore, comprehensive information on cell and molecular biology, physiology and genetics is available and the European Bacillus community (BACELL) has a well-established reputation for applying
Bistable switches are the key elements of the regulatory networks governing cell development, differentiation and life-strategy decisions. Transcriptional noise is a main determinant that causes switching between different states in bistable systems. By using the human pathogen Streptococcus pneumoniae as a model bacterium, we will investigate how transcriptional fidelity and processivity influence (noisy) gene expression and participate in bistability. To study this question, we will use both