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- Targeting BFL-1 for the treatment of cancer
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- Analysis and reporting of whole genome sequencing data from malaria parasites
- Analysis of long read data from the minION, with application to malaria
- Analysis of short tandem repeat markers from whole genome sequencing
- Antibody longevity following Plasmodium vivax infections
- Antigenic diversity of malaria parasites: towards more effective malaria vaccines
- Biogenesis of eosinophil granules
- Biological sequence analysis and genomic variant discovery
- Biology of the unique intra-mitochondrial bacterium Midichloria mitochondrii
- Characterising regulatory T cells in coeliac disease
- Chemical probing to identify effectors of necroptotic cell death
- Computational systems biology of Wnt/cell adhesion signalling in colon cancer
- Controlling apoptotic cell death in cancer
- Deciphering mechanisms of thrombocytopenia (low platelet count) in blood cancers
- Defining molecular signatures of drug resistance and sensitivity
- Designing immunotherapy for brain cancer
- Developing non-invasive methods to monitor kidney transplant rejection
- Discovery and analysis of autoimmune regulators
- Discovery of novel drug combinations for the treatment of bowel cancer
- Drug targets and compounds that block growth of malaria parasites
- Dying to survive: mechanistic insights into human bowel cancer development
- Dynamic discovery of innate immunity through imaging and genomics
- Dysregulation of TNF expression in inflammatory diseases
- Effects of nutrition on immunity and infection in Asia and Africa
- Elucidation of long range methylation structure using nanopore sequencing
- Eosinophil activation
- Eosinophil death
- Eosinophil heterogeneity
- Eosinophil maturation
- Epigenetic regulation of systemic iron homeostasis
- Epigenetic regulation of the immune system
- Explosive cell death and human disease
- Export of malaria virulence proteins during liver infection
- Function of proteins involved in invasion of erythrocytes by malaria parasites
- Functional genomics to improve therapeutic options for rare cancers
- Giardia duodenalis phosphoproteome and protein kinase network
- Harnessing the immune system to target small cell lung cancer
- Home renovations: understanding how Toxoplasma redecorates its host cell
- How do malaria parasites traverse human cells and invade hepatocytes?
- How does the malaria parasite prevent the host liver cell from dying?
- Human monoclonal antibodies against malaria infection
- IL5 signalling in asthma
- Identification of genes critical for the control of chronic infections
- Identification of malaria parasite entry receptors
- Identifying new cell death and inflammatory pathways
- Identifying proteome signatures of high grade glioma for precision medicine
- Insight into the cytotoxic T cell immune synapse
- Investigating apoptosis control in tumour blood vessels
- Investigating brain abnormalities with single cell ‘omics
- Investigating mechanisms of cell death and survival using zebrafish
- Investigating the mechanics of platelet formation
- Investigating the molecular regulation of neovascular eye disease
- Let me in! How Toxoplasma invades human cells
- Long-read sequencing for transcriptome and epigenome analysis
- Machine learning analysis of mutagenesis datasets
- Macro-evolution in cancer
- Mapping human gene mutations affecting anti-malarial drug efficacy
- Mechanism and modulation of K+ channels and membrane transporters
- Mechanisms of disease relapse in acute lymphoblastic leukaemia
- Microbiome analysis using long read nanopore sequencing
- Molecular mechanism underpinning dendritic cell ontogeny and functions
- Molecular mechanisms of innate immune signalling
- Next-generation mucolytics to treat lung diseases
- No sex please, we’re inhibited: searching for drugs to prevent malaria transmission
- Novel biomarkers and mechanisms of antimalarial drug resistance
- Novel real-time, quantitative imaging approaches for studying malaria
- Novel regulators of JAK-STAT signalling in development and disease
- Novel tool for malaria surveillance and intervention
- Optimising serological markers of recent exposure to Plasmodium vivax
- Quantitation of human T cell responses in primary immunodeficiency
- Reconciling intracellular imaging and metastatic behaviour in cancer cells
- Reconstructing the immune response: from molecules to cells to systems
- Role of protein glycosylation in malaria virulence
- Statistical bioinformatic analyses of RNA-seq and ChIP-seq data
- Strategies mammalian cells use to survive without growth factors
- Structural and biochemical studies on Notch signal transduction
- Structural and functional analysis of malaria invasion
- Structural biology and binding studies of BCL-2 family proteins
- Structural studies of invasion processes during malaria infection
- Structural studies of the Plasmodium and Toxoplasma tight-junction complex
- Target identification of potent antimalarial agents
- The role of glycosylation in malaria vaccine design
- Towards a molecular description of plasma cell diversity
- Tracking the spread of malaria in the Asia Pacific region
- Transmembrane control of type I cytokine receptor activation
- Uncovering the roles of long non-coding RNAs in human bowel cancer
- Understanding resistance to apoptotic cell death
- Understanding the common through study of the rare
- Understanding the development of humoral immunity to malaria
- Unravelling cellular circuitry with single cell RNA-seq and CRISPR
- Unravelling the molecular architecture of killer T cells in disease
- Why is interleukin-11 elevated in acute myeloid leukaemia?
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Marco Herold-Projects
Researcher:
Elucidating a role for the pro-survival Bcl-2 family member A1 in cancer
The pro-survival Bcl-2 family member A1 (the human counterpart is called BFL1) has been implicated in diverse cancers, including various leukaemias as well as lymphomas and melanoma. We have developed a conditional A1 knockout model and approaches to delete A1/BFL-1 in cell lines. We will use these tools to define the role of this pro-survival protein in the development and sustained growth of different cancers.
Post-translational regulation of A1 in vivo
The pro-survival BCL-2 protein A1/BFL1 is subject to stringent post-translational regulation culminating in degradation by the ubiquitin dependent proteasomal pathway. In collaboration with Dr Ingolf Berberich from the University of Wuerzburg, Germany, we have recently identified an E3-Ligase, which is responsible for A1 ubiquitination. We have developed new models to study the impact of the loss of this A1 E3-Ligase within the whole organism. Furthermore we have recently started to exploit whole genome editing screening tools to identify other/ additional components of A1’s destruction machinery. Once candidates are identified, we will use genome editing technologies to generate new models to study their impact on A1 stability in vivo.
Regulation of the pro-apoptotic BH3-only protein BIM
The pro-apoptotic BH3-only BCL-2 family member BIM is a key regulator of the haematopoietic system. Surprisingly little is known about the regulation of this pro-apoptotic BCL-2 protein. In order to unravel critical regulatory mechanisms of Bim RNA transcription and stability, as well as BIM protein stability we are performing overexpression and CRISPR/Cas9 screening experiments. In pilot studies we have already identified several interesting candidate regulators of BIM pro-apoptotic activity that are currently being validated. Moreover, we are also investigating Bim mRNA and BIM protein regulation in human cancer derived lines when they are treated with diverse chemotherapeutic agents. The aim of these studies is to identify the signaling cascades that induce BIM’s pro-apoptotic activity with the ultimate goal to harness these processes to develop improved cancer therapies.
Identification of novel tumour suppressor genes and oncogenes by CRISPR/Cas9 library screens in vivo
p53 is the most important gene in human cancer, which is mutated in 50% of human cancers. However, little is known about its tumour suppressive function. In order to identify the critical tumour suppressive pathways induced by p53 we are performing whole genome CRISPR/Cas9 screens in vivo.