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Deposition: In the past two weeks my work has mostly been full of dealing with structures. The first thing I needed to do was deposit some structures of ALK2 co-crystallised with three drug molecules that I had solved for our collaborators Swen Hoelder and Liam Hudson at ICR, who had been developing compounds against ALK2. Read More …
As you are probably aware by now, if you’ve read a few of my blogs, we are testing ATP competitive inhibitors to inhibit ALK2 but not any of the other 6 ALK family members. Thus, most of our activity and cellular assays test ALK2 as well as ALK5 activity in order to check the specificity Read More …
Hello there! This week I won’t be filling you in on my latest experiment, because instead I spent three days at the first ever Cancer Research UK Brain Tumour Conference held in the Royal Society of Medicine in London! (Also the biggest conference I’ve been to so far). The conference gathered over 30 great speakers Read More …
One of the more unpredictable parts of crystallography is also one of the most fundamental – will the protein crystallise? Despite decades of work done on protein crystallisation, and numerous ‘tricks of the trade’ to maximise the chances, whether a protein will actually form a crystal is still relatively random. With ALK2 we’ve crystallised it Read More …
Aside from having high potency towards ACVR1/ALK2, inhibitor compounds ideally should be highly selective and not target other members of the Transforming Growth Factor beta (TGFb) superfamily. TGFBR1/ALK5 is selected for off-target screening because of its potential role in cardiac functions. Firefly luciferase is transcribed downstream of ACVR1/ALK2 in BRE reporter plasmid and downstream of TBFBR1/ALK5 in CAGA reporter plasmid. Renilla luciferase is constitutively transcribed Read More …
It’s been a little while since I posted. I’ve been really busy, but haven’t had that much to report. I’ve been doing some processing of the fragment screening data we have so far. We found one possible hit in the pocket we are looking at for allosteric ligands, which initially looked very exciting, but on Read More …
It’s usually a good idea to have more than one trick up your sleeve… So with that in mind, I’ve started developing another viability assay for my DIPG cell lines. The first assay relied on convincing a cell line that naturally grows as floating spheres to grow stuck down on the bottom of plastic wells, Read More …
New compounds developed by Meds4Kids (M4K) and other collaborators against ALK2 would benefit from being crystallised so we can look at the structure of the complex and explain exactly how these compounds bind. This helps us work out how to improve them for both potency and selectivity and explain why some bind better than others. Read More …
Hi, my name is Ellie Williams and I’ve been working at the SGC since 2010 in the lab of Alex Bullock. I’m funded by FOP Friends to look at the development of new drugs that target ALK2 and to study the disease Fibrodysplasia Ossificans Progressiva (or FOP). In the last couple of years a new Read More …
I was away on leave last week, but happily, before I left, I set up 25 crystal plates of ACVR1 with various compounds. The details of the protein purification, the compounds used and some of the crystals obtained are here, on Zenodo. So I was able to at least come back to something after my Read More …
