A growing team of groundbreaking scientists around the world are now sharing their lab notebooks online
Further down the line I want to be able to test the activation of the BMP signalling pathway downstream of the ALK2 receptor. For this I plan to use the alkaline phosphatase gene as a readout – it’s a well known gene activated downstream of BMP signalling so a lot of easy to use assays Read More …
Hello everyone and happy New Year! I really, really wanted to end the year on a high note in December before I went off on holiday, but as it turned out, I didn’t have enough time to set up 18 plates and write a blog post on the last day. So I’ll just have to Read More …
In an effort to develop clinical compounds for Diffused Intrinsic Pontine Glioma (DIPG) treatment, new analogues of ACVR1/ALK2 inhibitors are continuously synthesised by Ontario Institute for Cancer Research (OICR) and Charles River Laboratories (CRL). I will provide prompt feedback of the cellular assay results to guide their design of new compounds. I determined the potency Read More …
Hello again! A few posts ago (here), I presented one fragment bound at the interface between two subunits of the HAO1 tetramer (figure 1 will refresh your memory). Our idea to optimize this fragment into an inhibitor would be to make it bigger so that it disrupts the HAO1 tetramer. I would expect this to Read More …
One problem with working with the isolated kinase domains of ALK2 and it’s type II binding partners, is that the affinity between the kinase domains alone is insufficient to allow complex formation. We know that the two proteins associate with each other in vivo and are co-localised by the domains on the outside of the Read More …
Hi there! The last month of my life was taken over by making sure my PhD first year report was beautifully polished, but I have returned with results of a small compound screen: These are all compounds that Jong Fu has already tested with his assays so we know they effectively inhibit ACVR1, but I Read More …
We are part of ALS-RAP, the ALS (Amyotrophic Lateral Sclerosis) 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. ALS, also called MND (motor neurone disease), is a group of diseases that cause Read More …
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: Read More …
Things have been really busy in the lab the last few weeks. I’ve done a couple of purifications of ACVR1 (ALK2), which I’ll post in Zenodo (getting loads of protein now), but probably won’t write up the details of every purification every single time anymore, as it’s the same process every time for this construct. Read More …
This week one of the things I’ve been working on is the final set of mutations in the GS domain of Alk2 to help us unpick the influence of phosphorylation on function. That, however, is a bit of a mouthful so let’s unpack it a bit. I said in my last blog post that we Read More …
