Introducing the team: The Gileadi Group in Oxford.

Hi! I’m Opher Gileadi, I head a group at the Structural Genomics Consortium (SGC) in Oxford. For many years, we’ve been looking at proteins involved in human. We’ve looked at a wide variety of proteins: from DNA repair enzymes and transcription factors to enzymes involved in signalling. In most cases, we focus on early work: structure determination, activity assays, antibody generation, and finding initial small molecule “hits”. Having the right reagents are the key to enabling new drug targets; we expect that our data will allow – or encourage – further work by medicinal chemists and biologists to seriously test therapeutic hypotheses (we call our data and reagents sets TEPs – Target Enabling Packages).

My team and I will be blogging and sharing our experiments on three areas of interest:

Alzheimer’s disease: We are funded by the NIH through the AMP-AD project (Accelerating Medicines Partnership – Alzheimer’s Disease). The project has integrated data from brain autopsies and model systems to identify new possible protein targets for treatment or prevention of Alzheimer’s (annotated in the Agora web site, run by SAGE Bionetworks. Our group is generating TEPs for some of these targets – we’ll share our progress in future posts.

ALS (Amyotrophic Lateral Sclerosis): We are part of ALS-RAP, the ALS reproducible antibody platform. We’re addressing one of the big conundrums to biomedical research: the lack, or the poor quality, of many antibodies used for research ranging from cell biology to histopathology.

Together with colleagues in Stockholm and Montreal we aim to validate a set of antibodies to 30 proteins involved in the disease. We will test commercial antibodies as well as generate new ones through phage display technologies.

Chordoma: Chordoma is a rare type of cancer that occurs in the bones of the skull base and spine. It is resistant to all forms of chemotherapy; patients are treated by surgery and radiation, but recurrence is common and, eventually, untreatable. A unifying molecular characteristic of chordoma is overexpression of a variant of the transcription factor T-Brachyury (TBXT), which is essential for survival of the cancer cells. Joseph Newman in my group has solved structures of the human Brachyury protein (PDB codes 6F58, 6F59); we are working together with groups in the University of North Carolina and in Baylor College (Texas) to explore TBXT as a drug target.

That’s all for today – we’ll follow-up with stories in these three areas.

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