There are many prizes for cultural activities, of which science is one. This week has seen the announcement of the Nobel prizes, a little earlier the IgNobels were awarded. There are, of course many other prizes. I have decided to set up my own.
A question that bugs me and which loomed large while I read the excellent review by Ding Xu and Jeff Esko from UCSD on “Demystifying Heparan Sulfate–Protein Interactions” is how many extracellular proteins are there?
This is an important question, since the interaction of extracellular proteins with heparan sulfate is absolutely central to cell communication, development, homeostasis and many diseases (cue: read that review). Experimental data take a good while to acquire and then be reproduced and validated. The field is extremely welcoming and inclusive socially, so I thought there is another way: open a book and award a prize.
Rules of entry
1. Deadline for entries is that date in the future when we agree on the number of heparan sulfate binding proteins in Homo sapiens.
2. To avoid argument over the actual number, a protein will be defined as the product of a gene, and encompass all splice variants, posttranslational modifications, etc.
3. To avoid further argument over the number (knowing the field, we love an argument, in the best sense of the word), an extracellular protein is a protein (see 1) that is demonstrated to at some time, in some tissue of the human body, in development, health or disease, to occur outside the cell. This is a geographical definition, not topological, so a protein exclusively in an intracellular membrane compartment is classed as intracellular.
4. The interaction of the protein has to be demonstrated directly. This may be done by biochemical means in vitro or by analysis of cells/tissue using mass spectrometry, advanced microscopy or the technique we would all happily flog our souls for, but has yet to be invented.
5. ANYONE can enter, even the organiser. This is a truly Open Access science prize. However, only one entry per individual is allowed. NSA, GCHQ, KGB Black Hats et al. will be employed to check that there is only one entry per person – they have your MAC addresses, IP addresses, etc., are paid by the taxpayer and so are responsible to you. Therefore, you can be certain that this will prevent any cheating.
The Prize
A beer. If you don’t drink alcohol, St Christopher or similar, if you do, then what I consider to be the lead beer of your country. You may suggest and the organiser will agree, on a singular output of a specific brewery, only if this is a small (≥250 employees) outfit.
Verification of the quality and value of the prize
I accept that it may be a while before the prize can be awarded. Therefore, I will undertake the onerous task of checking periodically that the prize is worth winning, through a process of random sampling.
The entries
I reckon that the number is around one third of extracellular proteins, and after a huge number of calculations I have come up with: 1757 heparan sulfate binding proteins encoded in the genome of Homo Sapiens.
What is your number?
Rest assured that I will be soliciting entries at every forthcoming meeting on the subject that I attend, and unlike the Ancient Mariner, I will stop everyone, not just one in three. You may, wisely, decide to avoid my “glittering eye” and enter your number below in the comments section. Your choice.
Ferniglab Blog 
Dave: I would argue that knowing all of the HSBPs is not really the important question, the issue is how many HSBPs depend on HS for activity or at least show a significant increase in activity or supramolecular organization when engaged with HS. I estimate this factor to be 0.3 based on our frustration in demonstrating that binding translates into something measurable in the biological world. Thus, one should multiply the total number of HSBPs discovered through binding studies or in silico work by ≤0.3. So 1757 x ≤0.3 = ≤527….given the level of my confidence in obtaining sufficient funding to actually resolve this problem, I would round it to ≤500.
Jeff,
The Prize Organising Committee (POC) accepts both your entry and your excellent argument, but is of the opinion that the scalar is close to 1. Resolution of this matter may require the administration of a further prize in due course, which will be discussed at future meetings of a subcommittee of the POC. The name of this subcommittee has yet to be established, as are its remit and membership. This will be the task of the SubCommittee for Advanced Thinking (SCAT).
I would agree with Jeff that the more interesting number will be those that are functionally relevant. No doubt there will be arguments over beers about what is a functionally significant effect, but from the known list of HSBPs (nice to see that terminology used rather than HBPs) there are already examples of (probably) non-specific ionic interactions, which would not be too surprising for such an anionic molecule. So I think the scalar will definitely be <1, but probably higher than 0.3. I would go for 0.42, since I suspect it is a somewhat metaphysical argument anyway, and that number is exactly 100 times the answer to the ultimate question of the meaning of life, the universe and everything (Douglas Adams, Hitchhikers Guide to the Galaxy) and thus has a pleasing ring to it. So my marker is 738 (assuming 1757 is correct for the extracellular HSBP interactome !).
A caveat – is there any reason we should limit the HSBP interactome to the extracellular sphere ? There is increasing evidence for possibly functional interactions of intracellular proteins with HS e.g. in trafficking, so this could add to the
Finally, as I don't expect to live long enough to accept the prize, and assuming the POC will make posthumous awards, if I win I will bequeath it to surviving members of the Turnbull clan.
Jerry,
Intracellular partners may indeed have to factored in, though teasing out specificity in the jungle of intracellular polyanionic polysaccharides (DNA, RNAs) will be fun.
You will be relieved to know that POC, forward thinking as ever, has already agreed that The Prize may be transferred in the manner you suggest. Moreover, POC has also considered the associated issue of The Prize counting as a taxable element of an estate. While this has yet to be resolved, if this is the case, POC will transfer to a suitable offshore location. I am assured that this strategy will allow inheritance of something as valuable as The Prize without any negative financial impact.
Of all prizes that a human being could give to another human being, surely this one would be the most venerated? The ultimate informational molecule in the known universe……..Indeed, it’s a lovely review by Jeff, raising more questions than it answers. Given how many of these intersections are actually clinically interesting is my particular bag, I come to this from a very particular angle……Agree with Jeff that the utterly maddening lack of correlation between binding and functional output is enough to drive one to the asylum….such that I believe in the “enigmatic” properties of the association. I think it’s more like 0.6-0.7, purely on the basis that we don’t yet have the resolution/time-loaded bandwidth needed to uncover all the short-range effects. My guesstimate is ~1100. My clinical guesstimate for exploitables, however, is 37!!!!! Not Hitchhikers existentialism, but rather Python existentialism………….