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Posts Tagged ‘polysaccharide’


Of nanoparticles, cells and polyanions

It is the end of semester 2 so it’s marking season. Since we double mark (a good thing), the final year research projects are marked by both supervisor and an assessor, a member of staff who is not involved in the project. One of the projects I marked was Gemma Carolan’s on “How do SmartFlares RNA detection probes reach the cytosol? Available are the PDF of report, and posts here and here.

I had a sense of déjà vu while reading the project – the clear endosomal location of the SmartFlares, regardless of the DNA sequences brought me back to the days when antisense was the technology of the future for medicine.

While evaluating new technology it is useful to go back and look at other high flying technology. The reality is that it takes decades before we know whether the promise (and hype) were justified; this is true for any hot topic from stem cells to nanoparticles and graphene.

Antisense effects can be mediated by RNAse H, an enzyme that specifically cleaves RNA-DNA duplexes and which protects our cells from RNA viruses. There are other mechanisms, e.g., interference with splicing or translation, but the RNAse-H mediated transcript degradation should be central to many antisense effects. There were many papers reporting specific effects (evidenced by differences between sense, antisense and scrambled oligonucleotides sequences). These certainly contributed to success of individuals and of institutions, e.g., in UK Research Assessment Exercise and grant awards.
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Congratulations to Quentin Nunes, who today successfully defended his PhD today. His first paper from his thesis work was published in late 2013 in Pancreatology. This was an analysis, using public datasets of mRNA expression data, of the putative heparin-binding protein network in the healthy pancreas and in pancreatic digestive diseases. The latter part of his thesis work will be submitted for publication soon (watch this space!) and is a proteomics analysis of heparin-binding proteins in mouse pancreas and in a mouse model of acute pancreatitis.

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Virginie’s first paper on her thesis work, “Network based meta-analysis prediction of microenvironmental relays involved in stemness of human embryonic stem cells” was published yesterday at PeerJ. She first put it up as a preprint (v1 here
revised v2 here and then submitted it – my first experience of this and something I will certainly do again.
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There are many prizes for cultural activities, of which science is one. This week has seen the announcement of the Nobel prizes, a little earlier the IgNobels were awarded. There are, of course many other prizes. I have decided to set up my own.
A question that bugs me and which loomed large while I read the excellent review by Ding Xu and Jeff Esko from UCSD on “Demystifying Heparan Sulfate–Protein Interactions” is how many extracellular proteins are there? (more…)

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Kat’s paper on the interactions of neuropilin-1 with a heparan sulfate mimetic library of modified heparins is now published in The PeerJ
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Ruoyan’s paper on “Diversification of the structural determinants of fibroblast growth factor-heparin interactions; implications for binding specificity” has been accepted for publication at the Journal of Biological Chemistry. The heart of her PhD thesis, this paper takes a hard look at the specificity of the interactions of six FGFs spanning five subfamilies with heparin and allied polysaccharides. She dissects the sites in the FGFs that are responsible for binding the sugars using the “Protect and Label” approach and the sites in the sugar that the FGFs binds using a combination of DSF, SRCD, biosensors and sugar libraries. As ever in biology, in important regulatory interactions there isn’t one binding site, instead these FGFs recognise what are best described as families of consensus sites in the sugar. Specificity in these consensus binding sites is elegantly illustrated by PCA and specificity maps to the evolutionary relationships of the FGFs.

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A rather interesting video, courtesy of William Birch at IMRE, which suggests that zebrafish can detect CS released by injured fish and that this causes a fear response. Makes sense, in that injury to skin would release CS and uninjured fish would want to move away from whatever has bitten the injured fish.

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