Thursday last week (Feb 27) Mark was up from Keele and popped his head around my office door – not a surprise, as he is often here to do circular dichroism on various heparin-binding proteins – to announce that Marcelo had managed to make some SARS-CoV-2 S1 receptor binding domain. Mark had asked Hao, my postdoc, to do some SPR measurements to see if it bound heparin.
Later in the day I went over to the SPR/CD lab to find Courtney, Mark’s PhD student and Mark beavering away on the CD. A quick discussion. Hao had finished some work on our first grade A heparin functionalised SPR surface, so we set about injecting the SARS-CoV-2 surface protein (Spike) S1 Receptor Binding Domain – a one shot experiment, as amounts of protein were limited, so we injected 1 mL at 500 µL/min (I like high flow rates as mixing is way better, though still far from perfect).
Bingo.
Still the control to do, since though confident in the surface’s resistance to non-specific binding, we still needed to be sure. So we collected the effluent fraction with the Receptor Binding Domain and then passed that through the pump (we are still sorting out fluidics etc., instrument only arrived a month ago) onto the reference channel (streptavidin, no heparin). Small drop due to mismatch in refractive index of the receptor binding domain and the running buffer, and then nothing. Back to running buffer and we go to baseline, no binding.
We agreed we should write up the experiments and put them out as a preprint. The work was not done in a vacuum. SARS-1 receptor binding domain binds heparin and its interaction with cellular heparan sulfate looks to be important in viral adhesion and cell entry (as for many viruses) and the corresponding region of the SARS-2 protein is identical. As we note in the preprint, this may provide a route to first line therapy, while we await a vaccine and other therapeutics.
The experiments depended on many other factors, which are worth considering, when we think about how research and innovation actually occur.
Back in the day, I had a suite of IAsys optical biosensors – brilliant instruments, with a vibrostirrer so we had proper mixing and never had issues with mass transport. The company bit the dust sadly, so these became legacy and then were scrapped. As a back up a colleague had a Biacore, but that packed up too. Personally I never liked these, as they are too ‘closed’ and I much prefer instruments that are open, without any ‘black box’ or inaccessible elements. Last year a new colleague, Roy Goodacre, hosted a seminar by Jean-François Masson from Montreal on SPR. So I went along and was taken by the instrument Jean-François had developed – open architecture in terms of fluidics, small, portable (he developed it to measure explosive residues in ground water used by communities near Canadian Army ranges). We had a chat after the seminar, and I contacted the company he has set up to commercialise the instrument. Some months later, when I had the time, I went around the Biochemistry Department with my hat and we put together the cash and bought a P4SPR, delivered end January 2020. I then set out plumbing in fluidics and making biotinylated oleyl ethelene glycol self assembled monolayers on the gold surface, with help from Richard Nichols in our Chemistry department who has a plasma cleaner.
So a group of people happy to work together with no discussion regarding ownership etc. and willing to stump up a few £ to buy a modest, yet powerful piece of kit. This really boils down to trust in your colleagues, be they PhD students or Professors and it is a real pleasure to work at ground level in such an environment. It is also an environment where you can innovate, something that still excites me.
Ferniglab Blog 
[…] to determine if this is actually the case takes time. It is nearly a month since the the team’s initial preprint (now updated with low molecular weight heparins), which was the first demonstration of an […]