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 »
Posted in Food | Tagged sorbet, strawberry |
The Sulfation issue of Essays in Biochemistry is out. This has its origins in the excellent September 2023 SUPA 2023 meeting, supported by the Biochemical Society and organised by Jon Mueller and colleagues. The entire volume is worth reading, as it covers a lot of new ground and ideas, starting with the sulfate anion itself in physiology through to sulfated cellular products.
Our own contribution was a review on the interactions of heparan sulfate with proteins and one on polysaccharide sulfotransferases. It has been 16 years since we wrote a review on the first topic and since there have been substantial advances. We took the opportunity to build up from the basics to some new(ish) ideas on the selectivity of these interactions and how they may control the diffusion of heparan sulfate-binding proteins in the extracellular space. Polysaccharide sulfotransferases are pretty much terra incognita. They occur across the Tree of Life, yet the majority of our data are on the mammalian Golgi enzymes; putative enzymes are the overwhelming majority in this field!
In the summer I started my engagement with Dulce Papy-Garcia’s department in UPEC; my relationship to the department goes back to the mid 1990s and I have always found it to be a most stimulating environment. It transpired that her Group had undertaken a massive analysis of the enzymes involved in heparan sulfate biosynthesis and from that had elaborated an exciting new hypothesis regarding its regulation, which amongst other things explained the counter intuitive phenotypes of a number of genetic disorders. I emailed Jon Mueller to ask if there was still space in the sulfation issue of Essays in Biochemistry – there was, so with Dulce we set about knocking their analysis into the shape of a review. The result was the third review which provides a new model to explain the phenotypes that result from genetic variation in the genes encoding the enzymes and transporters involved in heparan sulfate proteoglycan biosynthesis.
Reviews at Essays in Biochemistry are subjected to peer review, and for all three of these reviews the comments were both incisive and useful, allowing us to improve the articles. So a thank you to the reviewers for taking the time to read our submissions and provide us with the benefit of your ideas and insights. Another great plus is that Portland Press’ electronic proofing system is a pleasure.
Reviews do take a substantial effort, so now it is time to return to those drafts of primary research papers and finish them!
Posted in Alzheimer's, Biochemistry, Chemistry, Conference, Fibroblast growth factor, Glycobiology, Sulfotransferase | Tagged Glycobiology, glycosaminoglycans, heparan sulfate, proteoglycan |
Some months before @robField’s tweet setting off the train that led to the Eu sensor that discriminates PAP/PAPS, Ed Yates and myself were having a curry with Dulce Papy-Garcia from UPEC, who had examined one of our PhD students. A matter we discussed at length was ‘why sulfate’. That is, why does biology use both sulfate and phosphate to modify post synthesis proteins, polysaccharides and other molecules. We didn’t come up with an answer, but the conversation led Ed and myself to consider that the question merited exploration.
This we thought would be a simple matter.
It turned out to be one of the most difficult papers Ed and myself have written, to the extent that after N drafts (where N is a significantly larger number than either of us had experienced in any previous writing exercise) and too many summers we still had nothing satisfactory. So, we cunningly inveigled two colleagues, Tim Rudd from NIBSC and Marcelo Lima from Keele to join us on what we advertised as the sunny beach of sulfate and phosphate, but which in reality was a rather dank quagmire. There is though something about strength in numbers, and with very helpful input from Steve Butler in Loughborough, we arrived at what we considered a satisfactory synthesis. Happily, the reviewers concurred, and the paper is now published at Royal Society Interfaces, “Phosphorylation and sulfation share a common biosynthetic pathway, but extend biochemical and evolutionary diversity of biological macromolecules in distinct ways”.
This is by no means the last word on the matter, but along with some previous thoughtful papers we cite (if we have missed one, please let me know) it provides some ideas that may help us to understand why biology co-opted particular elements from the inorganic world to perform groups of functions vital to life as we know it now.
Posted in Biochemistry, Chemistry, Fibroblast growth factor, Glycobiology, Sulfotransferase | Tagged Fibroblast growth factor, glycosaminoglycans, heparan sulfate, kinase, phosphorylation, research, science, sulfation, Sulfotransferase |
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!
Posted in Biochemistry, Chemistry, Glycobiology, Scientific progress, Sulfotransferase | Tagged glycosaminoglycans, heparan sulfate, high-throughput, research, science, Science progress, sulfation, Sulfotransferase |
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:
Continue Reading »Posted in Biochemistry, Covid-19, Research integrity, Science process, Scientific progress, Universities | Tagged covid19, Long Covid, research, SARS-CoV-2, science, Science progress |
So today I sent this email as a reminder to the members of my research team.
“I write this email because University management has abdicated all responsibility towards the wellbeing of their staff and students, and their families. Current University and UK government Covid ‘rules’ contradict the most simple evidence, which is based on exceptionally solid physics and biology/medicine. We are scientists capable of critical thinking, and we should carry these qualities into our daily lives.
Continue Reading »Posted in Covid-19, Higher Education, Politics, Universities | Tagged science |
The UK schooling system is an example of the mirage of choice and how the mantra of ‘choice’ is used to reduce choice, opportunity and promote ideology.
Continue Reading »Posted in Education, Higher Education, Politics, Universities | Tagged Academy, Choice, Comprehensive, Faith, Grammar, School |
After an interaction on Twitter with a colleague who is associated with #LongCovid and #TeamClots, he asked me for some references. I thought what to send, and then realised that references plus something a bit more than a Tweet might be useful, so here goes.
Continue Reading »Posted in Biochemistry, Covid-19, Fibroblast growth factor, Glycobiology, Nervous system, Viruses | Tagged glycosaminoglycans, heparan sulfate | 2 Comments »
We have until June 23rd to submit this form to our GP to prevent the sale of medical information that is identifiable back to the patient (that means you) to 3rd parties.
Thanks to Byline Times for the tip!
The sale of such information is part of the Grand Sale of the NHS, which has been taking place since Thatcher came to power in 1978. A quick check of the effectiveness of health systems around the world will show that the private sector is not able to deliver adequate healthcare. Indeed the profit motive and the Hippocratic Oath are hardly compatible.
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.
Continue Reading »Posted in Higher Education, Science process, Universities | Tagged research, Research Excellence Framework, science, Science progress, Teaching |
My current list of major unforced errors by the Johnson government that have led to the covid disaster that is now 15 months old and shows little sign of letting up.
1. No enforced quarantine for international travellers, starting in March 2020.
2. Allowing both Liverpool away and home matches in March.
3. Allowing Dido Harding to go ahead with Cheltenham races.
4. Locking down too late in March 2020 and no control over interactional travel during 1st lockdown.
5. Not implementing a full mask policy by March 2020, when aerosols were known to be main rout of transmission.
6. No measures at transport hubs such as airports, railway stations, major bus terminals, e.g., thermal imaging cameras: not perfect, but will stop symptomatic travellers.
7. Failing to beef up NHS testing and instead spaffing cash on private sector testing.
8. After 1st lockdown, continuing to allow international travel, rather than focussing on supressing virus: Scotland was 2 weeks, England ~1 months away in July 2020.
9. Late lockdown in November 2020.
10. Early release of lockdown in December = early Christmas for virus.
11. Continued absence of proper border controls for travellers and one month late in putting India on red list.
12. Reversal of school mask policy, despite deep understanding of aerosol transmission, and no implementation of rules on air exchange determining number of people in a room.
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