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DPhil Student Matthew Holland Featured in Tatler Magazine after Presenting The Boat Race on BBC One

He finds parallels between explaining science and rowing. Both may seem complex at first, but breaking down basic principles can simplify understanding.

NLRP3 Inflammasome “DUBbed” by UCH-L1, affecting IL-1β production macrophages and microglia

Activation of the NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome complex involves association with ubiquitin C-terminal hydrolase 1 (UCH-L1). UCH-L1 chemical inhibition and deletion interfere with NLRP3 assembly and IL-1β production in macrophages and microglia.

CMD Study Discovers Unexpected Noncovalent Off-Targets of Clinical BTK Inhibitors

BTK inhibitors are a cornerstone of clinical anticancer therapy thanks to their strong and sustained effect on key disease-driving oncogenes. A new study by the Huber lab in collaboration with the Brennan and Fedorov groups at CMD, as well as Ivan Ahel’s lab at the William Dunn School at Oxford, reveals that these drugs exhibit unexpected off-target activity against non-kinase proteins that is independent of their reactive warhead.

Discovery of Conformationally Constrained ALK2 Inhibitors

The Bullock's lab, in collaboration with Ontario Institute for Cancer Research (OICR) and M4K Pharma, has published a study in the Journal of Medicinal Chemistry about the discovery of conformationally constrained ALK2 inhibitors.

Research team receives $25m Cancer Grand Challenges award

A global, interdisciplinary team of researchers, including the Centre for Medicines Discovery’s Professor Frank von Delft, has been selected to receive a Cancer Grand Challenges award of up to $25m over five years to tackle the solid tumours in children challenge. The Cancer Grand Challenges PROTECT team is led by Professor Stefan Pfister of the Hopp Children's Cancer Center in Heidelberg.

ASAP Discovery Consortium wins 2023 FASEB Dataworks prize

The AI-driven Structure-enabled Antiviral Platform (ASAP) has won an Exemplary Achievement Award from the Federation of American Societies for Experimental Biology (FASEB) and the National Institutes of Health (NIH). The prize recognises data practices in biological and biomedical research labs during the active phase of research.

Alzheimer’s disease: Protein-protein interaction inhibitors for MSN and CD44

Researchers have delved into developing small molecule inhibitors targeting protein-protein interactions in Alzheimer's disease.

The C2 domain of SHIP1 as an allosteric modulator of phosphatase activity

Publication explores the mechanism by which the C2 domain of SHIP1 is able to modulate inositol 5-phosphatase activity, providing insights into potential methods of targeting the protein to understand its role in Alzheimer’s disease.

Latest research at CMD identifies mutations in the BTB domain of KCTD15 that perturb BTB oligomerisation and cause a distinctive frontonasal dysplasia syndrome

Study identifies de novo missense variants in KCTD15 associated with frontonasal mass phenotype.

The solute carrier SPNS2 recruits PI(4,5)P2 to synergistically regulate transport of sphingosine-1-phosphate

The Dürr and Sauer group's new publication reveals export of immunoregulatory sphingosine-1-phosphate is regulated by the signaling lipid PIP2 via its action on the transporter SPNS2.

Discovery of a chemical probe for CDKL5 demonstrates role in hippocampal CA1 physiology

Mutations in CDKL5 cause a severe neurodevelopmental disorder. A recent paper in eLife reports the first chemical probe for CDKL5 that reveals new insights into the roles of CDKL5 in synaptic plasticity and human neuropathology.

Research reveals basis for KEAP1-CUL3 E3 ligase assembly and inhibition by CDDO

Bullock group's recent paper uncovers structural basis for KEAP1 assembly with CUL3 and offers a new generalizable TR-FRET assay platform that defines the contributions of different domains to their binding affinity.

Research reveals the first molecular understanding of BIRC6 – an essential regulator of cell death

Latest research has uncovered at the molecular level how BIRC6 (a giant ubiquitin ligase) keeps cells alive.

FOP Friends lab visit

The Bullock group was delighted to welcome the FOP Friends charity and patient families to the CMD in October. FOP (fibrodysplasia ossificans progressiva) is a congenital syndrome of extraskeletal bone formation caused by a gain of function mutation in the ACVR1/ALK2 protein kinase. Families were given a lab tour and updated on the latest research news, including progress of the “STOPFOP” clinical trial developed by the Bullock group and collaborators.

The Rainwater grant has been signed

The Rainwater Charitable Foundation announces partnership with drug discovery teams at the University of Oxford.

Congratulations to our DPhil student Amber Truepenny

Massive congratulations to our DPhil student Amber Truepenny who won the inaugural Jamie Ferguson Chemistry Innovation Award. It’s a real testament to all her hard work on an exciting and challenging project - watch this space!

Congratulations to DPhil student Eva Dalietou

Congratulations to DPhil student Eva Dalietou, Bullock lab, for winning the best poster prize with her work showing how cofactors bind to the KLHL12 E3 ligase at the Ubiquitin & Friends Symposium 2022, which was organised by the University of Vienna’s SFB Targeted Protein Degradation program.

Disease-associated KBTBD4 mutations in medulloblastoma elicit neomorphic ubiquitylation activity to promote CoREST degradation (new paper published)

The Bullock lab has a new paper in Cell Death & Differentiation entitled “Disease-associated KBTBD4 mutations in medulloblastoma elicit neomorphic ubiquitylation activity to promote CoREST degradation”. During normal development, CoREST complexes containing LSD1, HDAC, and CoREST silence chromatin. In medulloblastoma, mutations in the E3 ligase KBTBD4 induce CoREST degradation thereby promoting increased transcription of stemness genes for tumorigenesis. The study builds on a CRUK-funded collaboration between the labs of Vincenzo D’Angiolella, Steve Clifford and Alex Bullock.

Sequence and structural variations determining the recruitment of WNK kinases to the KLHL3 E3 ligase (new paper published)

The Bullock lab has a new paper in Biochem J entitled “Sequence and structural variations determining the recruitment of WNK kinases to the KLHL3 E3 ligase”. Structural, biochemical and cellular data reveal how the KLHL3 Kelch domain can accommodate the binding of multiple WNK isoforms and highlight a potential regulatory mechanism for the recruitment of WNK3.

Fragment Hotspot Mapping to Identify Selectivity-Determining Regions between Related Proteins (new paper published)

CMD, CCDC and Exscientia, and Oxford University collaborate on an automated, quantitative method for informing the design of compound selectivity across protein families.

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