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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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Len Harrison-Projects
Researcher:
Epigenetic regulation of T-cell function in health and disease
We have demonstrated differential microRNA (miR) expression and DNA methylation between human T cell subsets, and differences in these epigenetic signatures in naïve and natural regulatory T cells (nTreg) between healthy and T1D at-risk individuals. These studies have revealed new disease markers and mechanisms (e.g. genes that regulate T-cell function; Ezh2 methyltransferase function in T-cell differentiation) and are being extended to other immune disorders. This project comprises one or more sub-projects: 1) identifying the roles of specific genes that are differentially methylated in FOXP3 binding regions in nTreg, in healthy individuals and those with or at risk of immune-inflammatory diseases including T1D; 2) identifying changes in epigenetically modified genes during the development of T1D, and environmental factors that drive these changes, in conjunction with microbiome, metabolome and immunome studies; 3) defining the functions of Ezh2 and other PRC2 components in T-cell differentiation.
Team members: Yuxia Zhang, Gaetano Naselli, Len Harrison
CD52-Siglec interactions in health and disease
The role of CD52, a cell surface GPI-anchored glycoprotein, was unknown (except as a target of the CAMPATH monoclonal antibody) until we showed that activated T cells release soluble CD52 to mediate immune suppression by binding of its glycan to Siglec receptors. Binding requires co-interaction with the danger-associated molecular pattern (DAMP) molecule HMGB1.
This project comprises one or more sub-projects: 1) structure-function analysis of CD52-HMGB1-Siglec interactions in T cells and other immune cells, including X-ray crystal structure and glycan composition; 2) defining intracellular signaling pathways that mediate CD52-induced cell suppression and cell death; 3) in vivo studies of CD52-Fc including its therapeutic effects in laboratory models of immune-inflammatory disease (T1D, arthritis, encephalomyelitis, bowel disease, sepsis); 4) defining the immunosuppressive role of CD52 in the reproductive tract.
Team members: Maria Esther Bandala-Sanchez, Alana Neale, Katrina Ngui, Natalie Stone, Len Harrison
Does inflammation cause insulin resistance and type 2 diabetes (T2D)?
Over the last decade numerous laboratory studies have shown that obesity is associated with inflammation in adipose tissue and that agents that target this inflammation are therapeutically effective. Nevertheless, despite several clinical trials these agents have not been effective in humans with T2D. To identify novel therapeutic targets, we isolated inflammatory factors released from human adipose tissue. We have identified a factor that causes diabetes-like changes in cultured human fat cells. This project aims to define the mechanism of action of this factor and demonstrate that its inhibition prevents the development of insulin resistance and diabetes in laboratory models.
Team members: John Wentworth, Katrina Ngui, Len Harrison