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 work I’ve been doing (and which has been written about here as it’s happened) on looking at how the mutations in ALK2 effect the underlying activity of the kinase as well as effecting how well FKBP12 can inhibit ALK2.
The conference brought together 60 researchers in the field from around the world talking about a variety of different cancers but also other BMP related conditions such as FOP. Over three days there were some fantastic talks by the leaders in the field including from Dr. Caroline Hill from the Crick Institute in London who spoke about receptor cross talk in BMP signalling and how that might affect signalling through ALK2 and Prof. Eileen Shore from the university of Pennsylvania who spoke about mechanosensing and tissue stiffness in FOP.
I had a chance to get into some really interesting conversations with some of the attendees about the way their work and my work intersected and how we might be able to collaborate in the future – particularly interesting was talking to some Postdocs from Caroline Hill’s group who are looking at similar problems to me but from an in-cell perspective rather than using purified proteins. From that some interesting questions have been thrown up that I now want to test in my in-vitro systems and that will be detailed here as and when I’ve had a chance to try them. Hopefully this can lead to validation of both my work and theirs by complementing in-vivo and in-vitro approaches.
I thought it would be good to share the poster I created here – so you can find it over on Zenodo. It is designed for a scientific audience but not necessarily an FOP specialist audience so hopefully it should be fairly easy to follow. It leads the reader through the story of explaining that Gain of Function (GOF) mutations in ALK2 are involved in diseases like FOP and DIPG. I then go on to present data that shows that these mutations disrupt the binding of the inhibitor protein FKBP12 but that this isn’t the whole story (as regular readers of this blog will know). Then I talk about what I found out about what is needed for SMAD activation by ALK2 before looking at the increased phosphorylation of SMAD1 by the mutant ALK2 proteins compared to the wild type. This covers both the western blot data that shows more SMAD1 activation but also the mass spec data I’ve shared previously that looks at more SMAD1 and more ALK2 phosphorylation. Finally I showed the phosphomapping data on ALK2 that is starting to pick apart the exact phosphorylation locations on ALK2 that are necessary for SMAD1 activation (Also data I’ve talked about on this blog before). In this case it was nice to see that all the effort Rod and I had put into phosphomapping had paid off! Other groups had said they’d tried and been unable to map ALK2 using trypsin alone but our method of using 5 different enzymes both enriched and unenriched seems to have done the trick (despite it being 10x more work!).
There is great value from attending a conference like this and in this case I feel that I really did make some very important connections and had some very informative discussions that were directly relevant to my research and that will hopefully bear fruit in time and guide the direction of my experiments.