A growing team of groundbreaking scientists around the world are now sharing their lab notebooks online
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 …
I’ve put the Molprobity stats for the model I have refined to run my fragment screening datasets against in Zenodo. It looks pretty good, and I was happy when the parameters finally all went into the green. I have about 90 datasets with resolution lower than 2.6 Å, so hopefully I’ll get at least one Read More …
As mentioned in my Zenodo post here, I fine screened ACVR1 with the three compounds in the title. I got loads of hits for co-crystallisation with K62821a. I mounted almost two pucks’ worth of crystals (31 crystals) and sent them to Diamond for Monday’s run. Unfortunately, none of them diffracted better than 3.5 Å, so Read More …
Well, it’s been another week of not too much actual lab work and quite a lot of computer work. The lab work I did do was incredibly frustrating due to spending time searching around for reagents and then having a water problem with the liquid handler that is used to set up the fine screens. Read More …
I haven’t done that much lab work lately as I have been working on crystal data processing among other things. However, a couple of weeks ago I purified some ACVR1/ALK2 for crystallisation for fragment screening (which happened on Friday) and for co-crystallisation with some of our compounds. The experimental details are here, on Zenodo. As Read More …
ALK2 and ALK5 are Type I receptors on the cell surface that can be activated by specific ligands (illustrated in the diagram below). Once activated by ligand, ALK2 or ALK5 interact with Type II receptor to be phosphorylated (phospho-group chemically attached to the protein). Subsequently, ALK2 phorphorylates SMAD1/5/8 while ALK5 phorphorylates SMAD2. Phosphorylated SMADs then Read More …
Within a month (hopefully) I’ll be convincing C2C12 myoblast cells to express all kinds of mutant ALK2 to test its activity and interactions with other proteins within the cell. I’ll be doing this by treating them so that they’ll take up pieces of circular DNA (plasmids) that express those mutant proteins (i.e. transfecting them). Seeing Read More …
Background What is the link between a rare genetic disease that causes soft tissues to turn to bone, and a lethal childhood brain cancer? At first glance, with such different clinical phenotypes, it seems unlikely there could be any link, but it has been shown through whole genome sequencing of diffuse intrinsic pontine glioma (DIPG) Read More …
Hello world! I think I should let you know about the two diseases my project covers before we get started: Firstly, diffuse intrinsic pontine glioma (DIPG for short) is a childhood brain tumour that grows in a part of the brainstem called the pons. The disease progresses rapidly and the fact that it grows within the brainstem, and invades into nearby Read More …
