13:00: Welcome

Chairs

Jan Terje Andersen, the Laboratory of Adaptive Immunity and Homeostasis

Bjarte Reve, Nansen Neuroscience Network

Henrik Peersen, Norwegian Brain Council

Trim-Away: Targeted degradation of proteins and pathogens by TRIM21

Leo James

MRC Laboratory of Molecular Biology, Cambridge, UK

TRIM21 is a unique protein that is both an antibody receptor and E3 ubiquitin ligase. This combination of activities allows TRIM21 to protect cells from infection and makes it ideally suited for targeted protein degradation technologies (eg Trim-Away). By uncovering the molecular mechanisms by which TRIM21 labels its substrates and degrades them, we hope to understand its role in natural immunity and apply this knowledge to the design of new therapeutics.

The application of intracellular immunity for new therapeutic approaches in neurodegenerative diseases

William McEwan

Sir Henry Dale Fellow and UK Dementia Research Institute Group Leader UK Dementia Research Institute at the University of Cambridge, UK

Tau pathology is a driving feature of several common neurodegenerative diseases including Alzheimer’s disease. We find a critical role for intracellular immunity in limiting the spread of tau. We are advancing a deeper understanding of this active cytosolic defense for the development of new therapeutic approaches.

Type-I interferon exacerbates tau pathology by potentiating seeded tau aggregation

Sophie Sanford, PhD Student, McEwan Group

UK Dementia Research Institute at the University of Cambridge, UK

The antiviral type-I interferon (IFN-I) response is stimulated by the detection of virus-and damage-associated molecular patterns. Signatures of IFN-I-driven gene expression are observed in the brain of patients suffering from neurodegenerative diseases including Alzheimer’s disease. However, the role of IFN-I in the progression of tau pathology remains unknown. We demonstrate that the IFN-I response drives tau pathology by rendering neurons highly vulnerable to seeded aggregation. This identifies the IFN-I response as a potential link between amyloid and tau pathologies and as a therapeutic target for modulation of disease pathology.

15 min break

The ageing angle of Alzheimer’s disease and drug development

Evandro Fei Fang

Group Leader, Associate Professor, Department of Clinical Molecular Biology, University of Oslo and Akershus University Hospital

Ageing is the highest risk factor of neurodegenerative diseases, including Alzheimer’s disease. The Fang lab applies the hallmarks of ageing to untangle the aetiology of Alzheimer’s disease and for drug development. A few drug candidates developed are in clinical trials.

TRIM7 detects a C-terminal degron in human and viral proteins

Jakub Luptak

MRC Laboratory of Molecular Biology, Cambridge, UK

TRIM7 binds and degrades diverse substrates by recognising a simple dipeptide sequence at protein C termini. This means around 1% of the human proteome is a potential substrate as well as a range of viral proteins that are generated during polyprotein processing by 3C-type proteases. But what is TRIM7’s physiological role?

The seminar is organized by the Laboratory of Adaptive Immunity and Homeostasis, Nansen Neuroscience Network, Norwegian Brain Council, the Life Science Cluster and Norwegian Society for Immunology.