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- A multi-pronged approach to targeting myeloproliferative neoplasms
- A new paradigm of machine learning-based structural variant detection
- A whole lot of junk or a treasure trove of discovery?
- Advanced imaging interrogation of pathogen induced NETosis
- Analysing the metabolic interactions in brain cancer
- Atopic dermatitis causes and treatments
- Boosting the efficacy of immunotherapy in lung cancer
- Building a cell history recorder using synthetic biology for longitudinal patient monitoring
- Characterisation of malaria parasite proteins exported into infected liver cells
- Deciphering the heterogeneity of the tissue microenvironment by multiplexed 3D imaging
- Defining the mechanisms of thymic involution and regeneration
- Delineating the molecular and cellular origins of liver cancer to identify therapeutic targets
- Developing computational methods for spatial transcriptomics data
- Developing drugs to block malaria transmission
- Developing models for prevention of hereditary ovarian cancer
- Developing statistical frameworks for analysing next generation sequencing data
- Development and mechanism of action of novel antimalarials
- Development of novel RNA sequencing protocols for gene expression analysis
- Discoveries in red blood cell production and function
- Discovering epigenetic silencing mechanisms in female stem cells
- Discovery and targeting of novel regulators of transcription
- Dissecting host cell invasion by the diarrhoeal pathogen Cryptosporidium
- Dissecting mechanisms of cytokine signalling
- Doublecortin-like kinases, drug targets in cancer and neurological disorders
- Epigenetic biomarkers of tuberculosis infection
- Epigenetics – genome wide multiplexed single-cell CUT&Tag assay development
- Exploiting cell death pathways in regulatory T cells for cancer immunotherapy
- Exploiting the cell death pathway to fight Schistosomiasis
- Finding treatments for chromatin disorders of intellectual disability
- Functional epigenomics in human B cells
- How do nutrition interventions and interruption of malaria infection influence development of immunity in sub-Saharan African children?
- Human lung protective immunity to tuberculosis
- Improving therapy in glioblastoma multiforme by activating complimentary programmed cell death pathways
- Innovating novel diagnostic tools for infectious disease control
- Integrative analysis of single cell RNAseq and ATAC-seq data
- Interaction with Toxoplasma parasites and the brain
- Interactions between tumour cells and their microenvironment in non-small cell lung cancer
- Investigation of a novel cell death protein
- Malaria: going bananas for sex
- Mapping spatial variation in gene and transcript expression across tissues
- Mechanisms of Wnt secretion and transport
- Multi-modal computational investigation of single-cell communication in metastatic cancer
- Nanoparticle delivery of antibody mRNA into cells to treat liver diseases
- Naturally acquired immune response to malaria parasites
- Organoid-based discovery of new drug combinations for bowel cancer
- Organoid-based precision medicine approaches for oral cancer
- Removal of tissue contaminations from RNA-seq data
- Reversing antimalarial resistance in human malaria parasites
- Role of glycosylation in malaria parasite infection of liver cells, red blood cells and mosquitoes
- Screening for novel genetic causes of primary immunodeficiency
- Single-cell ATAC CRISPR screening – Illuminate chromatin accessibility changes in genome wide CRISPR screens
- Spatial single-cell CRISPR screening – All in one screen: Where? Who? What?
- Statistical analysis of single-cell multi-omics data
- Structural and functional analysis of epigenetic multi-protein complexes in genome regulation
- Structural basing for Wnt acylation
- Structure, dynamics and impact of extra-chromosomal DNA in cancer
- Targeted deletion of disease-causing T cells
- Targeting cell death pathways in tissue Tregs to treat inflammatory diseases
- The cellular and molecular calculation of life and death in lymphocyte regulation
- The role of hypoxia in cell death and inflammation
- The role of ribosylation in co-ordinating cell death and inflammation
- Understanding Plasmodium falciparum invasion of red blood cells
- Understanding cellular-cross talk within a tumour microenvironment
- Understanding the genetics of neutrophil maturation
- Understanding the roles of E3 ubiquitin ligases in health and disease
- Unveiling the heterogeneity of small cell lung cancer
- Using combination immunotherapy to tackle heterogeneous brain tumours
- Using intravital microscopy for immunotherapy against brain tumours
- Using nanobodies to understand malaria invasion and transmission
- Using structural biology to understand programmed cell death
- Validation and application of serological markers of previous exposure to malaria
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David Vaux - Research Projects
Researcher:
Determining the mechanism of lymphocyte apoptosis induced by glucocorticoids
In the mouse thymoma cell line WEHI-7, Flomerfelt and Miesfeld (JCB 1994) showed that there are at least six unique genes required for them to undergo apoptosis following treatment with dexamethasone. While they showed that the first gene in the path was the glucocorticoid receptor, they were not able to identify the other genes. We are re-visiting this system, using CrispR technology to identify the genes involved.
Regulation of autophagy by Bcl-2
We found that Bcl-2 is unable to inhibit autophagy in cells that lacked Bax and Bak, but when Bax and Bak were present, autophagy occurred as cells underwent apoptosis. This indicates that when activated, Bax and Bak can directly or indirectly promote autophagy.
We are seeking to determine the molecular pathway by which autophagy is induced in cells undergoing apoptosis.
Regulation of cell size and proliferation in the absence of apoptosis
Unlike their wild type parents, lymphoid (WEHI-7) and myeloid (FDM) cell lines lacking genes for Bax and Bak do not undergo apoptosis when treated with steroids or starved of IL-3. They shrink, arrest, and persist for weeks in a quiescent state.
These cells do not require autophagy, proteasome activity or protein synthesis to survive.
We wish to determine the mechanism for this arrest using CrispR screens, RNAseq, and CHIPseq.
These arrested cells are resistant to many chemotherapeutic agents. A drug that blocked this arrest might restore sensitivity to allow chemotherapeutic agents to kill cancer cells.
How does dexamethasone block cytokine growth signals?
Normally, factor starved arrested Bax/Bak deleted FDMs grow and proliferate as soon as IL-3 is added.
In contrast, FDMs arrested with dexamethasone do not grow and proliferate when IL-3 is added.
We wish to determine the mechanism by which the glucocorticoid receptor blocks signaling pathways activated by cytokines.