A growing team of groundbreaking scientists around the world are now sharing their lab notebooks online
Having previously purified BMPR1A (Alk3) and BMPR1B (Alk6), I spent some time purifying FKBP12 to form complexes with each of the receptors. FKBP12 binds to BMPR1A and BMPR1B via a similar GS domain to that seen in ACVR1, on the N-terminal side of the kinase domain and may help stabilize the structures and thus help Read More …
A large number of ACVR1/ALK2 inhibitors were previously synthesised by Paul Brenner’s team (Target Discovery Center, University of Oxford) for the purpose of treating Fibrodysplasia Ossificans Progressiva (FOP). Although these compounds were not designed with blood-brain-barrier permeability in mind, they can serve as good bench-marks for my cellular assays. Therefore, 30 of these legacy compounds Read More …
Dear readers, I had unfortunately torn my ACL for the silliest of reasons and have decided to use up my annual leaves for more time off. I will therefore be on hiatus till October. Adios! Jong Fu
Every summer my department holds a special mini-conference for the DPhil (aka PhD) students so that we can get to know each other and practice presenting our research. This year I took along a poster outlining my own project – Understanding the pathogenic mechanism of ACVR1 mutations in Diffuse Intrinsic Pontine Glioma – and presented Read More …
I had a couple of weeks off over August but I was back last week ready to crack on with work. As you’ve probably been following the ongoing saga, Ros and I have been struggling with expression of our key constructs. She had some good news on that on her latest post which has some Read More …
As I’ve mentioned in recent posts, our workhorse ACVR1 constructs have, for mysterious reasons, stopped expressing. This is clearly a massive problem, as with no protein we can not progress the project, and in the meantime, another DIPG patient has died, Aubreigh Nicholas, the 11-year-old girl who started the lemon face challenge. This is tragic, Read More …
In the absence of our “workhorse” protein, ACVR1 residues 208-499 (constitutively active Q207D mutant) (as we are still trying to work out why it won’t express at the moment), and the complete lack of crystals/diffracting crystals for the TGFBR1/FKBP12 complex, I have shifted to some other constructs we have to keep things moving. I had Read More …
As part of an ongoing collaboration with Meds4Kids Pharma (M4KPharma), we are testing a range of compounds identified and generated by them as being of interest in developing a molecule specific against ALK2 that has the right properties help treat some cases of DIPG. This also has significant implications for development of a drug that Read More …
I’m sad to report that a couple of test expressions later, we’re still no wiser as to why ACVR1 isn’t expressing. It’s worked on a couple of small scale expression test plates, but just doesn’t want to scale up anymore. We may be looking at having to remake the virus. In the meantime, I had Read More …
It’s been a very busy few weeks, a fair amount of lab work but also a fair bit of outreach work (which is the other part of my job) and so I’ve sadly neglected to write my poor blog post. However, now I’ve got the chance to write a bit about what I’ve been Read More …
