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Something rather different today and seasonal to boot. It is the strawberry season and pick your own does seem to result in the accumulation of very large quantities of fruit. I guess it always looks like less in a field. Indeed, there have been a few cries for help on Twitter and elsewhere, as people contemplate a huge pile of strawberries at home, wondering if they can possibly eat them. My late father had three excellent solutions.

In no particular order: Continue Reading »

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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.

 

A brace of sulfations


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!


ArrestAD

Our first results-driven scientific meeting was held in La Rochelle, France, on October 6 and 7. In addition to the research teams, we also had our two external advisors. It is important to have outside views on research and their substantial contributions were very much appreciated.

The UPEC group did a fantastic job in organising and structuring the meeting.  There was plenty of formal time for discussion, as well as time for informal discussions around the breaks, meal times and evening. The meeting itself covered the entire range of topics that lie within the ArrestAD programme. Talks included a recap of our objectives and strategy, administrative matters, ethics, and communication plans. The latter have an important ethical angle, as institutional publicity offices often oversell research. In the case of biomedical research, and perhaps very particularly to neurodegenerative diseases such as Alzheimer’s, over positive spinning of research results would likely be…

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‘flu and me


While reading and correcting a PhD thesis on ‘flu virus I thought I would check what strains I have encountered.

In February 1978 after playing a match for what was then RC Hermance (now HRRC) on a Sunday. I fell ill on the Tuesday, called home and was picked up by my mother.  Unfortunately, though a very smart person, critical thinking was not part of her education, which stopped at 16, and she dabbled in homeopathy. So I got sicker, spent 4 days at 41°C or above, but happily was then under our local GP (my mum was not daft) and was receiving anti-pyrogenic injections.  That time is a bit hazy, though my mother did say she thought she would lose me, so I must have been pretty ill.  This turns out to be an H1N1 virus, which only affected those under 26 years old. As this article  argues this particular ‘flu virus seems likely to have emerged from a lab (bio warfare) accident in the USSR or from vaccination (infection?) tests with live virus in China or the USSR, since the strain was almost identical to that from 26 years earlier and had not been seen in the wild in the intervening quarter century.

Fast forward to 1999 and I get a call from Tristan Bernard, past teammate at RC Hermance (now Life President, well deserved, a true evangelist for the sport) asking for a bed for him and a mate who were watching the World Cup; Liverpool was on a commute between games. A great evening, stated off in the Vines, and finished with a meal sometime after 2 am. A few days later ‘flu – this was I think brought to the UK by an Australian supporter and was an H3N2 strain virus. Not a major health incident for me though, a few days in bed and I was fine.

So the worst that rugby has done for me is ‘flu, twice, though I do have a wobbly ankle joint too.

As a side issue the murky past of the 1978 H1N1 ‘flu virus highlights the stupidity of allowing the gain of function engineering of pathogens. Regardless of whether the 1977 ‘flu virus did re-emerge from a lab, accidents, by definition, happen and viruses such as ‘flu remain an obvious war tool. I would be far more worried by N. Korean efforts in the molecular biology of viruses than by a few missiles with nuclear warheads. The latter can be stopped in flight, whereas viruses cannot.

On authorship


A discussion today with a student asking about the use of the Royal “we” in a report about his work. I agree, this is wrong. My suggestions were the first person singular and the passive. The passive gets a bad press in places, but it does work; the repetition of “we” or “I” grates, the latter particularly so because it can convey a strong sense of ego. Though as I pointed out, this depends how it is used. It was common in single author papers for the author to use “I”. The practice has disappeared due to multiauthorship and the urge to make scientific observations look objective. We finished by joking about the feudalism implicit in the use of ‘my laboratory’, as if this was some sort of sentient being, and then I wondered out loud whether one might not, in a multiauthor paper state:

“In experiment X (Fig. X), blogs demonstrated that….” And then later “In experiment Y (fig. Y) Doe indicated….”

Tonight a tweet from @UtopianCynic

UtopianCynic tweet

reminded me of my earlier conversation. Indeed, why bother with all the rubbish associated with authorship position? Why not have a list of authors and in the paper report who did what and who thought what?

It would then be clear (i) who pulled together the original hypothesis; (ii) who did the experiments; (iii) who thought up the interpretations of the data.

I think I might try this out.

This also solves the long-standing problem of blaming whoever is at the bottom of the pile when a paper is found to have manipulated data. Someone will be explicitly on watch and someone else will have done a particular measurement under that person’s watch.

It will be obvious who should walk the plank, and reaching for lawyers will only result in keel hauling, because it will be all written down and signed off.

 


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.

 


Past UK governments worked hard to bring the EBA and EMA to London, because of their knock on value to the wider economy, and two sectors in which the UK has some weight. The genius of Brexit has resulted today in the obvious: both are leaving London. The EMA goes to Amsterdam and the EBA to Paris.

I still wait for:

(1) A single piece of evidence that Brexit will provide the UK with opportunities.

(2) An admission of error from those who have publicly stated that the EMA and EBA would not be leaving London. Perhaps David Davis might step up first?