Real-time sulfotransferase assay

More sulfation

Earlier this year Simon Wheeler (who now has a well deserved substantive position, congratulations!) and Steve Butler published the first output from the BBSRC TDRI awarded to Steve, with myself and Ed Yates in supporting roles. It is always nice to collaborate with real chemists, as it reminds me I am very much a pseudo chemist, and I learn a lot. After what I would consider a quite heroic effort on the synthesis front, Simon and Steve pulled out a very useful sensor, based on a europium complex. The Eu sensor has good selectivity for PAP over PAPS, the universal sulfate donor. The assay works well and is very amenable to high throughput 384 well format assays (= more papers on the way). So we can now measure sulfotransferase activity in realt-ime independently of the acceptor for pretty much any enzyme-substrate combination. This represents an important tool for the wider sulfotransferase community. 

The paper also demonstrates the importance of social media in science, as a means to access in a non-direct manner new information that sets off an innovative project. I saw tweet from @Fieldlab highlighting a paper from Steve’s lab on lanthanide sensors able to discriminate nucleotide phosphates and read the paper. Naively I thought PAP/PAPS sensing using such compounds should be easy, so I contacted Steve. After some preliminary tests with PAP and PAPS on his side, we wrote the grant – another lesson here, as the application neared final from I went over to Loughborough for a meeting, which allowed us to iron out a few problems far more effectively than by electronic communication. The work was, as hinted above, far from straightforward, but like everything that is new, very rewarding and continues to be so.

I have just moved from the bird site to the proboscidean one and things look like there will be even more of such ‘random access’ of information there, so let’s see what turns up!

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Over? It hasn’t even started!

Where are we in the pandemic?

The bottom line here is that anyone making the statement ‘coming out of the Covid environment’ has not kept up with the data, which demonstrate the following:

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Some thoughts from an old fogey

What is important for your career in the Faculty of Health and Life Sciences at the University of Liverpool

With Project SHAPE progressing in the Faculty of Health and Life Sciences at the University of Liverpool, we have now moved onto the compulsory redundancy stage. As a senior member of staff who went back to the trenches after ten years in management, I have been contacted informally by a number of staff who have been sent a notice that they are at risk of redundancy. So I used my experience in management and my knowledge of the University to figure what may be important for retention in the Faculty of Health and Life Sciences at the University of Liverpool and, perhaps more important, what may kill your career and result in a P45.

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Withdrawing my labour

I made my first New Year’s resolution on December 31, 2013: to only undertake reviews for open access and learned society journals.  This I have stuck to well, as I noted a year later for the simple reasons that it makes sense and it frees up my time.

Today I had a request to review a manuscript for Nature Publishing Group’s Scientific Reports, and I realised that I need to clarify my position.

I am on strike.

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Can we evaluate ourselves without journals?

This is a question raised at the end of the excellent article by @Amy_Harmon regarding Open Access and preprints is can biomedical scientists evaluate each other without journals?

The short answer is a resounding yes.  Physical scientists and mathematicians have been posting much of their research as preprints on arXiv for a few decades, with no prejudice to their ability to evaluate the quality of work or of individuals.

The counter argument raised by many in biomedical sciences, from scientists to some journal editors can be boiled down quite simply: We are special and cannot possibly do this.

Various arguments are put forward, from competition (=fear of scooping) to intellectual property. These arguments are heard in many biomedical/biology departments, sometimes leading to quite heated discussions. It is also interesting to note that the defenders of the status quo are not necessarily the older members of the community.

There is a simple answer. Yes you are special, but not in the good sense of the word.

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We are afraid

A tweet brought me to a PeerJ blog post on the uptake of open peer review. The post is worth reading. At PeerJ open review is an option – authors and reviewers can opt in or out, and only if both opt in is the reviewing history of a paper published.  One thing that caught my eye was that while 80% of authors opt in, the total number of paper with open reviews is just 40%, which indicates that reviewers are more reticent.

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Open access and sci-hub: stumbling into the future

This post assembles various comments I have posted and other thoughts on sci-hub and access to the scientific literature. It finishes with some ideas about what we should consider keeping and some of my better experiences, as a consumer and producer of the scientific literature.

Some time between clay tablet and the PDF

Once upon a time manuscripts were hand written, double spaced (fountain pen as ever outperforming all other tools), graphs transferred to tracing paper using a rotoring pen and Letraset (also alive and well) used for symbols.

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Pubpeer & progress

During a quick scan this morning of the “recent” comments on Pubpeer, an activity that I pursue regularly, as part of my reading, there seemed to be a lot more author responses.  So I counted.

70 articles featured with comments.

10 of these had an author response.

This is progress. I have no data, but my impression is that a year ago author comments were far rarer, maybe 1% or thereabouts. Now we are at 14%. Let’s hope this is not an anomaly, but a trend, and maybe in a few years papers without author responses will be in the minority.

Regardless of arguments about anonymity, etc., post publication peer review is growing, which is a sign of health in the scientific enterprise.

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Groundhog day

Much has been written about the peer review process and its flaws. Richard Smith, a former editor of the British Medical Journal has stated that since peer-review doesn’t work, we shouldn’t do it

I have recently come across another example of the flaws in peer review. I reviewed a manuscript last year and identified what I believed to be technical problems and suggested at least major revision. The other two reviewers agreed; the three of us had homed in independently on the same technical issues.

Move forward a year and the paper is published in another (equally “prestigious”) journal, no changes.

So I will now amend my New Year resolution (still holding firm) from 2014 and 2015.

In addition to only reviewing for open access journals, I will from now on only review for journals where the review is open and published or where I am free to publish the review. That, at least, will avoid the ethical tension between participating in anonymous peer-review and then wanting to publish the critique when nothing has changed in the paper.

Why Groundhog day? This is not the first time I have had this experience.

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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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