Transcription and Translation

The Nobels are coming up. Here is last year’s prediction (note that I had listed Mello and Fire).Who will win this year? You tell me.

Some guesses for the Medicine & Physiology (or perhaps Chemistry) below the fold. Warning – the predictions presented here are highly biased towards cellular physiology.

Membrane Traffic. James Rothman and Randy Schekman. Maybe you could throw in Peter Novak.

There’s a rumour that intracellular signalling may win. Tony Hunter (phospho-tyrosine), Tony Pawson (protein signalling domains) and Allan Hall (small G-protein switches).

Structure of the first virus. Steven Harrison. (I’ve been told to throw in Michael Rossman from Purdue).

Structure of the ribosome. Tom Steitz, Venki Ramakrishnan, Harry Noeller and Ada Yonath. That’s one too many, but since most people would cross off one name, I’ll let you mentally eliminate the one who doesn’t belong.

Angiogenesis (very controversial). Judith Folkmann Judah Folkman.

Telomeres. Elizabeth Blackburn, Carol Greider and Jack Szostak. They won this year’s Lasker Award.

Major Histocompatibility Complex, structure, maturation etc. Very hard. Don Wiley would be nominated here but he died. There are many others. In addition you could nominate Peter Cresswell.

Stemcells. Ernest McCulloch and James Till (last year’s Lasker award.) very controversial – usually the science awards are not given to make political statements.

Transport Motors. Ron Vale (kinesin), Ian Gibons (flagellar dynein), Rich Vallee (cytoplasmic dynein and dynamin) … [there is little chance that this will happen - apparently the major complaint is that motors, i.e. myosin, already got recognized.]

And of course there is p53! There are about 3 codiscoverers (not sure about that). Bert Vogelstein wasn’t one of them, but he may get it too. (maybe for tumor suppressors??) If it’s tumor suppressors they could also give a tumour suppressor prize to Robert Weinberg.

OK time for some wild guesses …

i-436cc1f240fcc92ca7d627d73be8dcda-tsien2.gif

Fluorescent protein imaging technology. Perhaps this would be more of a Chemistry prize. Roger Tsien (Bapta, FLASH, and evolving about a dozen new fluorescent proteins from dsRed in vitro – see image above). This would kind of be neat as Dr Tsien used selection (i.e. evolution) to design reagents. (Take that you IDiots!) But then there is also green fluorescent protein (GFP). This would be a problem. Osamu Shimomura isolated this wonder macromolecule. Douglas Prasher cloned the gene that encodes it but lost his funding before he could do any work on the protein (and then left academic science!) Martin Chalfie heard about GFP (at a talk?) got the DNA from Prasher as his lab was closing. Chalfie published the first paper where GFP was used in some application. Tough to tell who they would give it to.

RNAi. It’s kinda early. Rich Jorgensen who first discovered it in petunias could get it. Then it becomes murky. Kemphues who accidentally made a mistake in worms can’t get it. Andrew Fire and Craigg Mello who figured out what was happening are the best choices. Other possible people are Ambrose, Zamore, Bartel, Hannon …

And yes .. the human genome. Venter, Landers, Collins. Not really a discovery. I like them, they did a lot of good. But I don’t think they should get it.

[And here's a real dark horse ... or black sheep ... Dolly or more specifically Cloning. Ian Wilmut would get it. Not likely in light of whatr happened in Korea.]

[2007 Update]
miRNA Very early. It would have to go to Vic Ambrose and Gary Ruvkin. But then again last year I thought that RNAi was early.

Transcription profile chips. Again more of a chemistry prize. Pat Brown would have to get it. This has revolutionized biology and may one day revolutionize medicine. One problem is that sequencing technology is so inexpensive that Affymetrix chips will soon be obsolete.On that note the latest sequencing technologies may get the Chemistry prize …

In vitro generation of Stem Cell Way too early. But Kazutoshi Takahashi and Shinya Yamanaka should get it one day. Click here to read why.
[end of update]

Any other suggestions?

Comments

  1. #1 MartinC
    September 25, 2007

    During the summer of 2006 we had a specially invited conference on functional RNAs here at the Karolinska with Craig Mello giving a keynote speech.
    This year a certain angiogenesis researcher was invited over.
    He is VERY well regarded over here and I wouldn’t rule him out.
    As for other contenders, Lynn Margulis (great insight – unfortunately went a bit mad before she won it rather than after, like Kary Mullis)
    Alec Jeffries, DNA fingerprinting ? Maybe the chemistry prize.
    Michael Behe – irreducible complexity ? (only joking!)

  2. #2 George Smiley
    September 25, 2007

    Innate immunity (sadly, Charlie Janeway died, and is ineligible). Agree that DNA chips won’t get it because with ultrahigh-throughput DNA sequencing chips will be obsolete tech within five years, maybe within three. Too early to give out a prize for ultrahigh-throughput sequencing, because it’s not yet clear which platforms will be the core tech going forward. Signaling: Robin Irvine and colleagues for discovering the IP3 pathway. Folkman won’t get it for angiogenesis because too many hated his ideas for too long, and may are still not convinced (of course, Pruisner is a counterpoint to that argument). Vogelstein is more likely. UPR: Peter Walter, who deserves it all the more because he did not share the protein targeting prize with his mentor, Blobel. Harrison is a good call, not least because of his long association with Wiley. You’re right that motors won’t get it, though Spudich, Vale et al. do lovely work. You’re an old cytoskeleton hand. How about Pollard/Mitchison/Kirschner? Membrane traffic – I’d bet against Novick, but I would not bet against Marino Zerial. Long shot: Rothman/Schekman/Orci. Watch the Scheckman and Rothman Lasker talks online to see the difference between graciousness and… well… anyway. Chaperones: Hartl and Neupert. Ribosome: Chem to Ramakrishnan and Yonath, Physiology to Noller and Steitz, I say. GFP: Tsien did not start the field, or even find the most important mutant (S65T), and other groups (e.g. at RIKEN in Japan) have made at least as many methodological/spectral contributions. If a GFP prize is awarded, it must go to Douglas Prasher of MBL/Woods Hole.

  3. #3 George Smiley
    September 25, 2007

    Martin – agree about Margulis. Smashing insight, once, but that insight was trumped by egomania, with emphasis on the mania part. Sadly, scores too many points here: http://www.math.ucr.edu/home/baez/crackpot.html

  4. #4 Larry Moran
    September 25, 2007

    Till and McCulloch get my vote. I expect all Canadians to write to the Nobel Prize Committee and urge them to award the prize for stem cells. :-)

  5. #5 bayman
    September 26, 2007

    I second Till and McCulloch. There’s nothing political about it, their discovery of hematopoietic stem cells in the bone marrow goes way beyond the current work and controversy re ES cells. Opened doors for bone marrow transplant medicine, understanding hemtopoiesis etc.

    Their work, done over 40 years ago, was radically ahead of it time and its hard to think of anything with a more fundamental relevance to medicine.

    Their classic papers make for a great read. Check out this one for a flavor:

    http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=14104600

  6. #6 George Smiley
    September 26, 2007

    Agree on the Till & McCulloch paper. Fundamentally, they applied a Luria-Delbruck fluctuation analysis to cell differentiation in hematopoesis. Real-deal genius – although they did not cite the 1943 L-D paper!

    Fluctuation tests:
    http://en.wikipedia.org/wiki/Luria-Delbrück_experiment

    Luria/Delbruk/Hershey Nobel Prize:
    http://nobelprize.org/nobel_prizes/medicine/laureates/1969/

  7. #7 RPM
    September 26, 2007

    And yes .. the human genome. Venter, Landers, Collins. Not really a discovery. I like them, they did a lot of good. But I don’t think they should get it.

    If francis collins ever wins a nobel prize I will kill myself shut down my blog post something very mean.

    And it’s “Lander”, as in Eric Lander.

  8. #8 RPM
    September 26, 2007

    oops! my html didn’t work out in that comment. “kill myself” and “shut down my blog” were supposed to be striked out.

  9. #9 bayman
    September 26, 2007

    George,
    Interesting connection there. Thanks for the info. I had wondered how it might have occurred to them to propose such an experiment…I guess you have to be creative when you’re trying to do cancer biology with a few mice and little else…

  10. #10 George Smiley
    September 26, 2007

    “I guess you have to be creative when you’re trying to do cancer biology with a few mice and little else…”

    Giants. We stand on the shoulders of giants.

  11. #11 apalazzo
    September 27, 2007

    Sorry for all the mistakes. Yeah, a nobel for cytoskeleton would be great … motors, mitosis or dynamic instability.

    OK I’m off to visit Firenze …

  12. #12 zatsuon
    September 28, 2007

    Physiology or medicine
    Elizabeth Blackburn and Carol Greider. Telomerase. (I think they are likely to win soon. Probably not Szostak, although he is a great scientist.)
    James Rothman and Randy Schekman. Membrane trafficking.
    Seymour Benzer. Neurogenetics.
    Ernest McCulloch and James Till. Hematopoietic stem cells.
    Leonard Herzenberg. Development of FACS.

    Physics
    Yoji Totsuka and Arthur McDonald. Neutrino oscillation.
    Yoichiro Nambu and Jeffrey Goldstone. Spontaneous symmetry breaking.
    Michael Berry and Yakir Aharonov. Berry phase and Aharonov-Bohm effect.
    Alain Aspect. Tests for Bell’s inequality.
    Makoto Kobayashi and Hidetoshi Maskawa. CP violations.

    Chemistry
    Harry Noller, Peter Moore, and Tom Steitz. Ribosome structure and mechanism. (Ramakrishnan is a possibility, but probably not Yonath.)
    Edwin Southern. Southern blot.
    Alex Rich and Paul Doty. Hybridization.
    Patrick Brown? and Steve Fodor? DNA microarrays. (Do you think they will be obsolete so soon?)
    But probably non-bio stuff this year to make chemists happy.

  13. #13 George Smiley
    September 28, 2007

    I agree that Szostak is a great scientist, a brilliant guy. But at least two of the developments with which he’s most closely associated, telomerase and SELEX, were pioneered by others: telomerase by Blackburn/Greider; SELEX by Larry Gold. Szostak’s more recent origin-of-life stuff with liposomes is courageous – really visionary – and if it pans out it could contribute to a future Nobel.

  14. #14 George Smiley
    September 28, 2007

    zatsuon, I probably overstated the case for sequencing obsoleting chips within five years, but it *will* dramatically reduce the importance of chips. Chips will continue to be useful in cases where you want, for example, a tiling array to look at origin firing in replication. But for studies of gene expression, I do think that sequencing will take over. The price of chips is not falling quickly (linear), and chip applications depend on chip *design*, which is expensive if you have an application not accomodated by an off the shelf chip. Part of the reason for the slow price drops is that Affy’s tech is too heavily patent-protected to scale down a lot further. Conversely sequencing does not require a priori probe design, its cost is falling fast (exponential), and it does not demand (as much) amplification of nonabundant material, which introduces all kinds of icky biases. And there are multiple, excellent, competing technologies. I’m really glad I’m not in the array business.

  15. #15 apalazzo
    September 29, 2007

    I am now in Siena and I am just checking up on the blog (and the latest from the Nobel noise – the winner will be announced Oct 8th).

    After thinking a bit about theprize (hey I have a good life here in the Tuscan countryside) it would be nice to have another cytoskeletal prize. But in addition to the list mentioned above I would like to add Shinya Inoue who discovered the mitotic spindle using polarized microscopy. A very critical discovery.

    OK this was a vacation away from blogging and labwork and so … arrivederci.

  16. #16 George Smiley
    September 30, 2007

    Yes! Shinya also (1) figured out that MTs are dynamic, and that solvent entropy provides the key driving force for MT polymerization; (2) co-invented modern real-time microscopy of cells and cytoskeleton (with Allen, Salmon, Jacobsen et al.), leading to the discovery of kinesin by Vale et al.; (3) was a key player in the early work on GFP.

    However, his lack of a Nobel (or Lasker, for that matter) is one of the pillars of my cynical worldview. Gawd forbid that I should have to change my worldview just so that a great scientist can get the recognition that he entirely deserves!

  17. #17 kobeboy
    October 2, 2007

    How about Mario Capecchi, Martin Evans and Oliver Smithies for homologous recombinations and knockouts in mice. Pretty useful technology for animal models of disease. And fairly extensively used.

  18. #18 ac
    October 2, 2007

    Put me down for Blackburn, Greider, Szostak et al.

  19. #19 MartinC
    October 8, 2007

    And the winners….
    Mario R Capecchi
    Sir Martin J Evans
    Oliver Smithies

  20. #20 larry
    December 31, 2007

    Conversely sequencing does not require a priori probe design, its cost is falling fast (exponential), and it does not demand (as much) amplification of nonabundant material, which introduces all kinds of icky biases