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Archive for the ‘Glycobiology’ Category


I have written the following to my Brexit Party Representatives in the European Parliament. At the heart of parliamentary democracy is the idea that our representatives do indeed represent the interests of their constituents, regardless of Party politics. Of course interests have to be balanced but when these are win-win, there can be no reason for not representing a particular interest. As the matter is not a personal one, then I have also put it on my blog, since there is no reason for secrecy.

I will, of course, post any further correspondence, unless it is confidential for some reason.

“Dear Ms Fox (& cc’ed to Mr Nielsen and Mr Bull)

I am writing to you as one of your constituents regarding an issue which affects me personally and the region. As a University Professor I have over the years been awarded research funds from various Framework Programmes. Most recently, I am part of the €4M FET-OPEN programme “ArrestAD”. This aims to test a new paradigm for Alzheimer’s Disease screening and lay the foundation for a new class of drugs that would arrest the disease.

FET-OPEN projects are very much blue skies and in our case we appear to have hit the jackpot. The trials of the diagnostic in Paris and Warsaw  are quite spectacular and our own work has shown that the targets which ArrestAD has proposed are eminently druggable.

ArrestAD is a 4 year programme. As in any blue skies research, towards the end of the penultimate year a decision is made by the research team whether we should apply for a new, larger project, under one of the translational programmes available under H2020, or to can the idea, in the event it isn’t going to deliver.

Since ArrestAD is delivering its promise, the team will be going forward and applying for a translational programme. This will involve further clinical centres and greater industry participation, since we need more patients and, for drug development, far greater resource.

Alzheimer’s being what it is, ArrestAD obviously impacts widely and not just on myself: there are substantial social and economic ramifications for our region, the UK, and beyond.

The problem we face is that with a so-called No Deal Brexit, the UK loses access to funding from H2020 and the future framework programme. There is no  legislation in the UK Parliament that would guarantee funding as a 3rdcountry. The upshot is that Brexit will prevent my continued contribution to this likely life-changing research programme. Importantly, it will prevent the UK from reaping economic benefit (clinical trials, pharmaceutical industry).

As my representative in the European Parliament, it is imperative that you work to find a solution, which ensures that the drug development arm of this project remains based in the UK, and that the UK is able to participate fully in the wider clinical trials of the diagnostic. I think you would agree that given the impact of this dreadful disease, this is in everyone’s interests.”

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Friday Pat Eyers pushed our two papers on new screens we have developed for sulfotransferases up onto Biorxiv. More about the history of this work later. For now the briefest of summaries.

The heparan sulfate 2-O sulfotransferase paper is here

and the tyrosine sulfotransferase paper is here.

The key messages are:

(1) Mimetics of PAPS, the universal sulfate donor, that inhibit sulfotransferases are present in kinase inhibitor libraries.

(2) We demonstrate selectivity, in that some compounds inhibitor one sulfotransferase better than they do the other.

(3) PAPS mimetics look like providing a rich vein of sulfotransferase inhibitors of varying selectivity, rather like ATP mimetics have done for kinases.

(4) We have two very effective high throughput screens, which means no sulfotransferase is now beyond our reach.

Sulfation has been frustrating due to the lack of chemical tools to selectively inhibit a particular sulfotransferase. With these two papers we can foresee such tools in the not too distant future and with these, we can unpick the role of sulfation in biology, from development, through homeostasis to disease.

Exciting times!

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Congratulations to Aiseta!

On Monday 4 December Aiseta Baradji successfully defended her thesis. A long journey and a hard one as ever with its ups and downs, surprises and a certain amount of head scratching over data that push us in new directions. In the end a great thesis that will be consulted in the labs of her supervisors for a long time. Now onto the next phase.

 

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Two postdoc positions are available in my lab.

Both are part of the larger, European Commission-funded FET-Open programme, ArrestAD, which has recently been funded.

Position 1 aims to characterise heparin-binding proteins in Alzhiemer’s disease.

Position 2 aims to develop inhibitors to Golgi sulfotransferases. (more…)

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ArrestAD

The ArrestAD team had its kick off meeting in Paris on 5 January 2017. This was held on Paris, the base of our coordinator, Dulcé Papy-Garcia and was hosted by the APHP in the Espace Scipion. Team members from outside Paris stayed at the Hotel La Demeure  situated nearby and though on the Boulevard St Marcel, nice and quiet.

The kick off meeting started with a presentation form our coordinator, which provided the backdrop for the day. Science presentations from the participants then followed. These provided an overview of the position of the field of the participant and then summarised research plans. In a multidisciplinary project, one cannot be fully up to speed with the other fields, so we all learned a lot. The more technical part of these presentations gave us an opportunity to discus the nuts and bolts of our research plans and how these fitted together. It…

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Changye Sun and Yong Li, who successfully defended their PhD theses in November have published a paper each in Open Biology on the interactions of fibroblast growth factors (FGFs) with glycosaminoglycans:

Heparin binding preference and structures in the fibroblast growth factor family parallel their evolutionary diversification

and

Selectivity in glycosaminoglycan binding dictates the distribution and diffusion of fibroblast growth factors in the pericellular matrix.

(more…)

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Our review on fibroblast growth factors (FGFs) as tissue repair and regeneration factors, which we made available as a preprint from the time of submission is now published at PeerJ. (more…)

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