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- A new regulator of 'stemness' to create dendritic cell factories for immunotherapy
- Advanced imaging interrogation of pathogen induced NETosis
- Cancer driver deserts
- Cryo-electron microscopy of Wnt signalling complexes
- Deciphering the heterogeneity of breast cancer at the epigenetic and genetic levels
- Developing drugs to block malaria transmission
- Developing new computational tools for CRISPR genomics to advance cancer research
- Developing novel antibody-based methods for regulating apoptotic cell death
- Discovering novel paradigms to cure viral and bacterial infections
- Discovery and targeting of novel regulators of transcription
- Dissecting host cell invasion by the diarrhoeal pathogen Cryptosporidium
- Do membrane forces govern assembly of the deadly apoptotic pore?
- Doublecortin-like kinases, drug targets in cancer and neurological disorders
- E3 ubiquitin ligases in neurodegeneration, autoinflammation and cancer
- Engineering improved CAR-T cell therapies
- Epigenetic biomarkers of tuberculosis infection
- Exploiting cell death pathways in regulatory T cells for cancer immunotherapy
- Finding treatments for chromatin disorders of intellectual disability
- Functional epigenomics in human B cells
- Genomic rearrangement detection with third generation sequencing technology
- How does DNA damage shape disease susceptibility over a lifetime?
- How does DNA hypermutation shape the development of solid tumours?
- How platelets prevent neonatal stroke
- Human lung protective immunity to tuberculosis
- Interaction with Toxoplasma parasites and the brain
- Interactions between tumour cells and their microenvironment in non-small cell lung cancer
- Investigating the role of dysregulated Tom40 in neurodegeneration
- Investigating the role of mutant p53 in cancer
- Lupus: proteasome inhibitors and inflammation
- Machine learning methods for somatic genome rearrangement detection
- Malaria: going bananas for sex
- Measurements of malaria parasite and erythrocyte membrane interactions using cutting-edge microscopy
- Measuring susceptibility of cancer cells to BH3-mimetics
- Minimising rheumatic adverse events of checkpoint inhibitor cancer therapy
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- Predicting the effect of non-coding structural variants in cancer
- Revealing the epigenetic origins of immune disease
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- Structural and functional analysis of DNA repair complexes
- Targeting human infective coronaviruses using alpaca antibodies
- Towards targeting altered glial biology in high-grade brain cancers
- Uncovering the real impact of persistent malaria infections
- Understanding Plasmodium falciparum invasion of red blood cells
- Understanding how malaria parasites sabotage acquisition of immunity
- Understanding malaria infection dynamics
- Understanding the mechanism of type I cytokine receptor activation
- Unveiling the heterogeneity of small cell lung cancer
- Using alpaca antibodies to understand malaria invasion and transmission
- Using combination immunotherapy to tackle heterogeneous brain tumours
- Using intravital microscopy for immunotherapy against brain tumours
- Using nanobodies to cross the blood brain barrier for drug delivery
- Using structural biology to understand programmed cell death
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Melissa Call-Projects
Researcher:
T cell receptor structure and function
The T cell antigen receptor (TCR) recognizes peptide fragments bound to major histocompatibility complex (MHC) proteins, activating T cells to kill target cells and/or secrete soluble factors. While the structural determinants of ligand discrimination are well studied, the mechanism by which receptor engagement outside the cell is sensed by signalling molecules inside the cell is still an open question. We are combining disulphide mapping and solution NMR techniques to determine how the eight-subunit receptor complex is arranged within the membrane and how transmembrane structure and dynamics relate to receptor activation.
Team member: Logesvaran Krshnan
DAP12-dependent NK cell receptor assembly and function
Natural killer (NK) cells are lymphocytes that eliminate cells exhibiting dysregulated MHC or otherwise altered cell-surface phenotypes, often due to viral infection or oncogenic transformation. A vast array of receptors governs the balance between NK cell cytotoxicity and quiescence, and many of the activating receptors depend on a homodimeric signalling module called DAP12 to supply cytosolic links to intracellular biochemical cascades. This project applies solution NMR and, more recently, lipidic cubic phase (LCP) crystallography techniques to examine the transmembrane structures adopted by DAP12 during assembly with “client” receptors.
Team member: Konstantin Knoblich
Regulation of cell-surface immune-regulatory proteins by MARCH-family e3 ubiquitin ligases
The levels of peptide:MHC complexes and other immunologically relevant proteins available at the cell surface can be modulated by regulatory proteins of the Membrane-Associated RING-CH (MARCH) family. MARCHs are integral membrane proteins with alpha-helical TM domains and cytosolic ubiquitin ligase domains. We use cellular biochemical and flow-cytometry based functional assays combined with solution NMR and lipidic cubic phase (LCP) crystallography techniques to study how MARCH proteins trap substrates through interactions with their TM domains. The major aim of this project is to identify what structural motifs govern substrate identification and thereby identify new substrates and molecular pathways that are MARCH-regulated.
Team members: Cyrus Tan and Raphael Trenker