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I’ve been lucky enough to have a student (Mira) in the lab working with me for the past few weeks and so I’d like to write about the work that we’ve been doing together. We spent some time cleaning up an old sample of ALK2 that Ros had left over in the freezer to set Read More …
In my last post, I told you I had soaked my follow-up compounds into HAO1 crystals to start developing structural explanations of how these compounds work. So far I have analysed four interesting protein-compound structures: 2 at the active site, 1 at the gating loop and 1 at the oligomeric interface. Full experimental details can Read More …
I’ve got a few things to catch up with on the blog – one of them is to talk about a conference I attended in Oxford recently. I attended the Biochemical Society BMP Signalling in Cancer II meeting which was held in St. Annes College, Oxford. At this meeting I presented a poster on the Read More …
Special thanks to: David Drewry – Helped with designing the nanoBRET tracers M4K pharma OICR chemist team – Synthesised the M4K1046-linker derivatives Carrow Wells (UNC) – Conjugated the M4K1046 to nanoBRET fluorophore Background: I have always wanted to establish nanoBRET target engagement assay for ALK5. Relative to dual luciferase promoter assay and immunofluorescent staining, nanoBRET Read More …
In this post I’d like to return to looking at my work on phosphorylation. Phosphorylation is a key signalling method for activating the BMP pathway and inducing activity. Specifically activation of ALK2 by phosphorylation leads to phosphorylation of SMAD1 which leads to gene transcription that ultimately is responsible for bone formation. In this post I’m Read More …
Did you know as many as 30% of the cells in labs could be misidentified? And what a nightmare it would be to find out years of your work are just completely wrong because you got your skin cells mixed up with your brain cells… So to avoid that catastrophe, I took some time to Read More …
ZFYVE9C (Otherwise known as SARA) is a scaffold protein involved in the association of various protein components as part of the TGFB signalling pathway. The equivalent in the BMP signalling pathway is a protein known as Endofin so studying SARA (which is slightly easier) might give us useful insights for both proteins. For more details Read More …
I’ve not posted in a while, mainly because things have been really busy, but good busy, as I now have 3 new datasets/structures, of ALK2 with M4K2118, M4K2149 and, amazingly, M4K2009. As you know, this is our lead candidate, which until now has not behaved very well in crystal trials, and it hasn’t been possible Read More …
A belated Happy New Year everyone! It has been a good while since my last post so I wanted to update you on what I have been spending 2019 on so far. After identifying some really promising follow-up compounds in my activity assay, the next step was to find out how they bind to HAO1, Read More …
I thought I’d spend a blog post just talking about the various paths of my research and try and tie it all together. A lot of my experiments do dot around these various arms of investigation and so one experimental post doesn’t necessarily tie in directly with the previous one or the next one and Read More …
