Congratulations Dr Alghrair

 

Today was the culmination of Zaid’s PhD journey, when he successfully defended his thesis on the use of gold nanoparticles to probe the mechanism of action of a peptide that inhibits ‘flu virus infectivity. Though he approached his viva with trepidation, his beaming face afterwards told a different story. The usual smattering of corrections, a paper already up on Bioarxiv ready to submit for peer review and another to put up on Bioarxiv, and in a few weeks he will be truly done, with a CV to match.

 

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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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Sphingomyelin-targetted gold nanoparticles

David Paramelle’s paper on using gold nanoparticles stoichiometrically functionalised with a peptide that recognises sphingolipids has just been published in Advanced Healthcare Materials (Publisher’s site; Pubmed)

The paper is the classic “Sunday afternoon” project, which arose through discussions with Rachel Kraut at NTU.

As ever, a lot more than Sunday afternoons ended up being put into the paper, because David had to develop some new approaches. Particularly nice was the purification of nanoparticles functionalised with the sphingomyelin-binding peptide (called “SBD”) from non-functionalised nanoparticles. This is a key step for the preparation of nanoparticles carrying just one functional peptide or group. Hitherto, we have happily had affinity tags as the functional group, which allows for affinity chromatography (examples here, here and here).

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Are we there yet?

The question relates to what Langmuir termed “Pathological Science”, simply put “people are tricked into false results … by subjective effects, wishful thinking or threshold interactions“. There is a lot of pathological science and I only use the examples below, because I am most familiar with them; for nanoparticles, I have a personal interest in understanding these materials, since I use them to try to make biological measurements, e.g., here.

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Covalent conjugation of proteins and sugars to nanoparticles

Dan Nieves’ paper on an easy and accessible method to covalently conjugate proteins, sugars and indeed pretty much any biomoleucle onto nanoparticles has just come out in Chem. Commun.

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A resolution growing firmer by the day: don’t be a commodity

On December 31 2013 I posted my New Year’s resolution: to only review manuscripts from open access or learned society journals.

My reasoning was that open access will only be the norm if we stop giving that which is most precious, our time, to closed access journals. I really think the wider community needs to start to be selective in reviewing. It is far easier to implement than the radical re-alignment of library journal subscriptions.

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How many silver nanoparticles have you got?

The sadly predictable hyping of things nano reached a nadir recently with the promotion of silver nanoparticles (aka “silver bullet”) as a treatment for ebola virus. There has been a great discussion of this and other aspects of silver nanoparticles by Andrew Maynard (here, here for ebola and here for the essential Risk Bites video).

It may surprise some, but until a few weeks ago, there was no simple, direct published method to quantify non-destructively silver nanoparticles. Yet, the non-destructive quantification of silver nanoparticles is essential to any experiment that aims to prepare and use these in a biological context. Without it any experimental work is likely to be qualitative and simple things, such as determining the stoichiometry of functonalisation, become difficult. Indeed, so important is simple quantification of nanoparticles that we validated and published a method for gold nanoparticles in 2007 that has been very well received by the community and which we use daily in the lab.

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The burden of proof

This post has been stimulated by a post on PubPeer entitled “A crisis of trust”
This post should be required reading for all engaged in research and in the management of the institutions involved in research, including funders and journal editors. I made a brief comment, relating to a sentence that is some way down the post:

“This could be done if together we invert the burden of proof. It should be your responsibility as a researcher to convince your peers, not theirs to prove you wrong”.

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Self-righting or sinking?

Inspiration for this post comes from various sources, including Arjun Raj’s posts on the STAP papers (here and here) and that by The Spectroscope (here)
and my previous posts on the question of whether science does self-right.

I take issue with the trivialisation of data fabrication.

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A birthday question

A rather one sided debate on stripy nanoparticles is taking place over on PubPeer and on Raphaël’s blog

An individual (“unregistered”) is engaging a good old Gish Gallop, having a hard squint in the dark and seeing patterns. It happens.

I have suggested that “unregistered” should turn their efforts to something more mundane, which is to explain the re-use of data across a number of paper from the Stellacci group.

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