whatever happened to the Orient Express?

The EuCheMS chemistry congress will take place in Istanbul next year, so I was wondering whether I could go there by train. The SNCF website says it doesn’t sell tickets to that destination. Deutsche Bahn can’t tell the price, but at least it gives me a connection.

Travelling from Frankfurt, it would take three nights, two days (55 h 50 mins total duration), and five changes to get there:

• Night train Frankfurt to Vienna (EN421)
• Vienna to Budapest
• Budapest to Beograd
• Night train Beograd to Sofia
• 10 hours wait in Sofia
• Sofia to Dimitrovgrad, Bulgaria
• Night train Dimitrovgrad to Istanbul

The first train, EN421 comes from Cologne, so the connection also works from there, as well as from other German stations including Bonn, Koblenz, Mainz, Würzburg, Nürnberg, Regensburg, Passau.

Deutsche Bahn very kindly gives me a connection from Paris as well, although it doesn’t even cross German territory. I could take a TGV Paris to Zurich, direct night train Zurich to Budapest, and then it’s the same as above for the rest of the journey (total: 60 hours). From London it recommends going via Brussels and Cologne, 63 hours.

I think the last change in Dimitrovgrad is where they lost me. I wouldn’t actually mind travelling three nights in a row and having some time to look at the cities in between. But Dimitrovgrad, population 38,015, not to be confused with the eponymous town in Russia, sounds random and a bit scary.

Whatever happened to the Orient Express? (I looked it up, the short answer is, it ceased to exist, the long answer is on Wikipedia.) Shouldn’t there be a direct line across Europe, linking all those new member states?

So, well, maybe I’ll skip this conference. Unless somebody has a bright idea? Are there any prospects for improvements in Bulgarian railways?

image source: wikipedia

Prague slide show

I spent a rather lovely week at Prague, checking out the EuCheMS conference and also spending a lot of time roaming the city in the footsteps of Kafka, Dvorak, Jacopo Strada, Tycho Brahe, Kepler ...

Here's a slideshow of a small selection of my photos:

intrinsically disordered proteins

Intrinsically disordered proteins in biomedicine, IRB Barcelona, 4.-6.10.2010

Some 13 years ago, Kevin Plaxco told me about an intriguing piece of research done by geneticist friends of his, involving a signalling protein that is exported through the hollow core of the bacterial flagella under construction, until the finished flagellum is closed off with a cap. Writing a News and Views commentary for Nature, we discussed this system as a prime example of a protein that has to be unfolded in order to carry out its biological function (The importance of being unfolded, Nature 386, 657-659, 1997, PDF).

We weren’t aware of any other literature specifically discussing this issue at the time (we missed one paper that had used the horrid terminology “natively unfolded” which we hadn’t thought of), but there were already a few examples of other proteins to discuss in this context. Incidentally, the geneticist authors of the paper we pegged our piece to weren’t very interested in the protein folding implications of their work, so we were free to take the issue and run with it.

The new field whose birth we assisted as midwives has grown quite remarkably in the years since, witness the recent research conference organised by the IRB Barcelona, “Intrinsically Disordered Proteins in Biomedicine”, attended by some 120 researchers and held in this rather wonderful building (The Institut d'Estudis Catalans in the centre of Barcelona, 100 metres away from Las Ramblas):



The conundrums that we already discussed in 1997, namely how can you tell that the disorder isn’t an artefact of your experimental conditions in vitro, and how can disordered proteins survive in the cell, are still being kicked around, although on a much higher level. And with more examples: there are now more than 1200 intrinsically disordered proteins (IDPs) listed in the database disprot.org.

The in vivo vs. in vitro question is now being addressed with a range of sophisticated methods that also allow in vivo studies of protein structure (and lack thereof).
To the stability question, an answer is emerging in the shape of the realisation that disordered proteins involved in signalling are often meant to be present only in small concentrations and for a short time.

Technical advances reported at the meeting included he “live” (though debated in discussion) observation of movements of a disordered chain by high-speed AFM, single molecule dynamics measurements by fluorescence, as well as variations on NMR, SAXS, and combinations between these two complementary techniques.

The biomedical applications promised in the title of the conference aren’t quite ready yet, though the fact that many IDPs work in transcription regulation suggests that their understanding will be useful for cancer research. Thus, the much-studied tumour repressor gene product p53 featured in several talks and posters. Amyloid-forming proteins such as alpha-synuclein also feature in the IDP roll call. Also, linear peptide motifs, recognition sites often found within intrinsically disordered regions, appear to serve as prime targets for viruses to mimic.

All in all, definitely a research field to keep an eye on, even though I have to admit sentimental bias when I’m saying this.

PS Other impressions from Barcelona (and Paris) to appear on flickr soon.