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Posts Tagged ‘chondroitin sulfate’


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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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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I went down to Birmingham with Chris Hill, one of the MSc students joining the lab for the summer to meet Barry Leadbetter, who has made seminal contributions to our understanding of choanoflagellates. Now that we are armed with genome sequences, these unicellular eukaryotes look very much to be the the descendants of the unicellular ancestor of metazoa. They have a tyrosine kinome, which is a hallmark of metazoa, since virtually all cell-cell communication in animals involves tyosine phosphorylatioin at some point, even though tyrosine phosphate only accounts for ~2% of protein phosphorylation in a mammalian cell. Even more exciting from our perspective, was the analysis done by Alessandro Ori, which identified genes in choanoflagellates that might encode enzymes for heparan sulfate and chondroitin sulfate biosynthesis.

Barry provided us with detailed instructions and, most importantly, the benefit of his years of experience of growing these animals. We brought cultures of M Brevicolis and of S Rosetta back to the lab and we now embark on the adventure of growing these creatures, with the aim of seeing if we can find biochemical evidence for heparan sulfate.

More information on these organisms here and here.

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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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