Proteostasis and Immune Signalling in Cancer and Dementia Image \nProfessor Kathryn Ball - Chair in Biochemistry and Cell Signalling Research in a NutshellProteostasis is a complex regulatory network which balances the cellular proteome by coordinating protein synthesis, folding, functional activity and degradation. Disruption of cellular proteostasis manifests in levels of proteotoxic stress that can compromise the immune system, initiate age related neurodegenerative conditions and predispose to cancer. We focus on defining the molecular and cellular mechanisms by which interferon regulated immune signalling and ubiquitin-mediated proteostatic mechanisms are integrated and coordinately regulated in order to protect cells and organs from aberrant protein:protein that re-purpose signal transduction pathways.Our current focus is cancers of high unmet clinical need and dementia with synucleinopathies, for example:Two major obstacles in the treatment of oesophageal cancer (OAC) are metastasis and drug resistance. We are using tissue proteomics to identify novel OAC targets and dissecting pro- and anti-cancer interferon regulated proteins in order to develop novel biologics with anticancer activity. We are also exploiting interferon and proteostasis dependent immune-blockade pathways to define novel therapeutic approaches.Dementia with Lewy bodies (DLB) is a protein disease with a high unmet need for novel treatments and progression models. We are using iPSC derived neurons and animal models to study the role of ubiquitin pathways, proteostasis and interferon signalling in DLB. Research Programme Image People Kathryn BallPrincipal Investigator and Professor of Biochemistry and Cell SignallingCatarina DiasPhD StudentJonas GasparaviciusPhD StudentJulia Mara KulbeErasmus InternFiona LickissVisiting Postdoctoral FellowJia NingPhD StudentAshita SinghResearch AssistantDr Filip TrckaPostdoctoral FellowContactKathryn.Ball@ed.ac.uk Kathryn Ball - Research Information CollaborationsDr Tilo Kunath, CRM (University of Edinburgh)Professor Ted Hupp, The Institute of Genetics and Cancer (University of Edinburgh)Professor Malcolm Walkinshaw, CTCB (University of Edinburgh)Professor David Argyle, Vet School (University of Edinburgh)Dr Alison Hulme, Chemistry (University of Edinburgh)Professor Bořivoj Vojtěšek, RECAMO, Masaryk Memorial Cancer InstituteDr Chandra Verma, A* SingaporeDr Robin Fahraeus, Universite ParisProfessor Krystyna Bieńkowska-Szewczyk, University of GdanskProfessor Rory Duncan, Heriot-Watt UniversityPartners and Funders RECAMO/European UnionMedical Research CouncilESRICAlzheimer’s Research UKScientific ThemesProtein structure-function relationships in vitro and in cells; cell signalling and proteomics in cancer; ubiquitin signalling and proteomics in dementia; generation of biologics for basic and translational research.Technology ExpertiseProtein structure and function; generation and use of both conventional and synthetic antibodies for basic research and translation into novel therapeutics; proteomics and mass spectrometry; interferon and antiviral cell signalling; cell and molecular biology; generation of cell models using gene editing; tissue biochemistry; imaging nano-probes and biosensors; chemical genetics. This article was published on 2024-09-23