Of nanoparticles, cells and polyanions

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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A prize worth winning: How many extracellular proteins bind to heparan sulfate?

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?

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Seminar on heparin and HS

Dr Marco Guerrini, Ronzoni Institute, Milan, will deliver a seminar entitled “NMR methods for characterisation of carbohydrate ligand binding” on Monday 12 November, 1 pm, Lecture Theatre 1, Life Sciences Building.

Dr Guerrini’s work, stretching over 25 years, has been concerned with investigating structure and function relationships in glycosaminoglycans. There are a biologically important family of structurally complex polysaccharides, which lie at the heart of many intercellular signalling processes, including those targeted in regenerative medicine and those disrupted in major diseases such as cancers and inflammatory conditions. His work also underpins our understanding of one of the lynchpins of modern medicine, the anticoagulant heparin. Highlights of Marco’s work have included the identification (in 2007-8) of toxic contaminants in pharmaceutical heparin, which had escaped the notice of regulatory authorities and lead to many deaths, and evidence exploding the myth of exquisite specificity in heparin-antithrombin interactions. Dr Guerrini ‘s talk will provide an introduction to this important class of polysaccharides, the principle methods that he uses currently, which are mainly NMR-based, but augmented by other complementary techniques, and will describe detailed structural studies of several interactions in solution. The talk will offer a rare opportunity to hear about interaction studies largely from the perspective of the saccharide ligand, which is often neglected, and will describe approaches that are highly complementary to the structural, functional and systems level studies currently being undertaken in IIB.

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