The Effector Detector and a Common Love of Science

I have a new name: the effector detector!

This has just appeared in The Scientist: Effector Detector, which is a kind of follow up on a paper that I my team and my collaborators published a couple of years ago in PNAS. 

I had a little advance warning that this commentary was going to appear, but didn't get the chance to see it or comment on it in advance. The coverage seems rather superficial, and it neglects the important role that our Japanese collaborator Toru Tobe (from the University of Osaka) played in the work, which was just as important as mine (if not more so). But it is nice to be noticed!

Another nice thing about our original PNAS paper, aside from the science, was the international character of the team, which included scientists born in the UK, New Zealand, Israel, Iraq, France and Japan drawn from Christian, Jewish, Muslim and Shinto or Buddhist backgrounds. As local Birmingham scientist Joseph Priestley (discoverer of oxygen and religious and political radical; statue in Birmingham shown left) said in 1793 of the Lunar Society of Birmingham:

"We were united by a common love of Science, which we thought sufficient to bring together persons of all distinctions, Christians, Jews, Muslims* and Heathens, Monarchists and Republicans."

*Priestley used the old-fashioned term "Mohammetans", but I have translated his sentence into modern English.

Dispatches from the cutting edge of flagellar biology, part 2

Following on from my previous post, the second set of take-away messages from Keiichi Namba's presentation last week all centre on the ATPase associated with the flagellar protein export system. But first some background...

Since the early 1990s, it has been known, from sequence comparisons, that the flagellar ATPase (FliI) is homologous to the alpha and beta subunits of the F-type ATPase, a transmembrane protein complex (see figure) found in bacteria, mitochondria and chloroplasts (see http://www.atpsynthase.info). 

In 2003, Nick Matzke (then at the NCSE and so a couple of years later science adviser to the plaintiffs in the Dover trial) wrote an essay summarising plausible evolutionary scenarios for the origin of the bacterial flagellum. He noted a couple of previous suggestions that the proto-flagellum might have originated from the F-type ATPase. Crucially, he predicted that additional homologies would be found between components of the F-type ATPase and the flagellar protein export apparatus, for example between the b subunit of the ATPase and FliH and between the delta subunit and FliJ. 

In 2006, I confirmed one of Nick's hunches through homology searches, showing that part of FliH was homologous to the b subunit. However, things turned out slightly different from Nick's predictions in that FliH is actual of a fusion of domains homologous to the b subunit and the delta subunit.

Last year Namba's group published the structure of FliI and confirmed the striking homology with the F-type ATPase enzymatic subunits. At that stage in the game, it had become clear that the ATPase was a universal component not just of flagellar export systems but also of non-flagellar type III secretion systems. Also, if it was also clear that if one knocked out the gene for FliI, one abolished flagellar biosynthesis. Thus, just about everyone in the field accepted that FliI was an essential component of the flagellar apparatus and that it energised secretion of proteins through the protein export system. In other words, if there were anything to the idea, put forward by Behe and others in the ID movement, that the flagellum showed "irreducible complexity", even experts might have accepted that FliI was one of the "irreducible" components!!

BUT earlier this year, Minamino and Namba (and independently a team headed by Kelly Hughes in the US) overturned all our assumptions by showing that it was perfectly possible to make flagella without FliI--what you needed to do was knock out FliH at the same time. Somehow or other FliH, which usually interacts with FliI, gums up the export apparatus in the absence of FliI. So, bang goes another pillar of support for the ID argument! In fact, it appears that flagellar protein export is powered not primarily by the ATPase by the proton-motive force. 

Anyhow, to get back to what Namba said at the Bristol meeting last week....

He provided a run through of all the work leading up to his recent Nature article on the dispensibility of FliI. I was then very proud to see him cite my paper on the FliH/F-type ATPase homology. But then he provided the final piece in the jigsaw (and Nick Matzke's ears should prick up at this point)!

Namba and colleagues have now solved the structure of FliJ, another protein that interacts with FliI and FliH. And what they found was clear evidence of homology with yet another protein from the F-type ATPase--the gamma subunit!

So, now we have deep and broad homologies between the flagellum and the F-type ATPase, just as Nick predicted. This provides another nail in the coffin of the idea that flagellum was intelligently designed. If the flagellum were the product of intelligent design, particularly by an omniscient deity, the designer could have custom-built it from scratch, so it need not resemble anything else in nature. By contrast, the processes of evolution tends to cobble together and tweak already existing components (something Francois Jacob called bricolage)--and slowly but steadily it is become clear that the flagellum has been built this way. 

There are now likely to be serious scientific payoffs--what all these homologies mean is going to occupy Namba et al for years to come, and it's a fair bet that comparisons between the two protein complexes are likely to clarify the structures and functions of both systems. 

Science rolls on while ID stays stuck in its non-productive rut! What we need more of is science!

Dispatches from the cutting edge of flagellar biology, part 1

Last week I attended the third UK type III secretion meeting, held at the University of Bristol. As with the two previous meetings, it encompassed a wide range of topics within the field of bacterial flagellar biosynthesis and type III secretion. For those of you not familiar with the field, the bacterial flagellum is the chief organelle of motility in bacteria and is related in structure, biosynthesis and evolutionary history to a molecular syringe known as the type III secretion system, which is used by bacteria to inject subversive "effector" proteins into eukaryotic cells. In both cases a complex macromolecular complex is assembled in the cell envelope, with proteins travelling through a central channel that spans two membranes and the periplasm.

The highlight of the meeting were keynote addresses by Keiichi Namba and his colleague Tohru Minamino on the structure and function of the bacterial flagellum. Tohru visited my group a couple of years ago, but I had not met Keiichi before, who has been at the cutting edge of the structural biology of the bacterial flagellum for over a decade. I had a chat with him over lunch. We briefly discussed the silly fuss that the "intelligent design" movement makes over the bacterial flagellum. When I asked him whether they had any problem with creationists in Japan, he just laughed and said, no, that was a problem only in America and Europe.

For more background on this issue, see Ken Miller's The Flagellum Unspun

and this movie of Ken:


and this paper by myself and Nick Matzke.

For me there were two take away messages from Keiichi's talk, one of which I will mention here, the other I will deal with in a subsequent post. Interestingly, Keiichi and colleagues are in the habit of getting superb videos made of their work every year or two, so in each post I will include (a link to) one of Keiichi's videos.

Watch this video from 2004 describing the work of Keiichi's Protonic NanoMachine Project (sorry for the link offsite, have tried and failed to upload it here). Remarkably, by then they had already achieved an atomic resolution structure that effectively spanned the whole flagellar filament (a structure visible by light microscopy!). 

In fact, the filament is part of a series of structures that form the axial components of the bacterial flagellum (filament; hook-filament junction; hook; plus the rod forming the protein export channel in the basal body). In Bristol, Namba reported that he and his colleagues now have structures for all the axial proteins. Interestingly, in every case, the structures show clear homology to one another and to flagellin, confirming earlier suggestions by myself and others that the flagellar axial filament has arisen by a process of successive gene duplications from a single progenitor protein. The way is now open to a detailed reconstruction of the steps leading to the evolution of the axial structures and even to resurrection and investigation of the original axial protein. 

This tremendous pace of advance in the mainstream scientific view of the bacterial flagellum (which accepts evolution as a given)  contrasts markedly with the poverty of the intelligent design viewpoint, which has spawned no new experiments or insights.