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TREM2: A TEP for Neuroscience & Neurological Disorders

The Target Enabling Package on #TREM2 for #AlzheimersDisease includes investigations on binding modes & functional activity of scFv antibody fragments. In collaboration with @ARUK_ODDI @karolinskainst @thesgconline @KTHresearch @EisaiUS & VivaBiotech.

Human AGR2 Deficiency Causes Mucus Barrier Dysfunction and Infantile Inflammatory Bowel Disease

The Bullock group is happy to contribute to this new report by Holm Uhlig @NDMOxford, Bernice Lo @SidraMedicine and colleagues describing the role of a missense mutant of AGR in the pathogenesis of inflammatory bowel disease #IBD

CDKL5: A TEP for Inflammation and Neuropsychiatry

CDKL5 harbours loss of function mutations causing a variant of #RettSyndrome, & may be a drug target for acute kidney injury. Our #CDKL5 Target Enabling Package (#TEP) shows structures (with inhibitors), in vitro assays, & functional analyses in C. elegans

The next release from our 2021 TEPs is TETRAN

A #TEP for inflammatory disorders. #MFSD10 (TETRAN in humans) may function as an organic anion efflux pump & a transporter for some #NSAIDs. The 2.6 Å structure is the first for a human atypical #SLC!

SLC14A1: A Target Enabling Package for Cardiovascular, Metabolic & Neurological Disorders

Our next Target Enabling Package is a #TEP for Urea Transporter B (UT-B; #SLC14A1) This TEP shows the structure of UT-B in apo and inhibitor-bound states, & confirms binding of an inhibitor molecule in vitro.

Selection and structural characterization of anti-TREM2 scFvs that reduce levels of shed ectodomain

Congratulations to DPhil student Aleksandra Szykowska on her new publication in the journal Structure describing the binding modes and functional activity of scFv antibody fragments that bind to the extracellular Ig-like domain of TREM2, a receptor expressed by microglia associated with an increased risk of Alzheimer's disease. We hope that the detailed characterization of their epitopes and properties will facilitate the use of these renewable binders as structural and functional biology tools for TREM2 research.