Mark Bollenbacher of Harvard Medical School (a postdoc in the lab of Prof. Roy Kishony) gave a talk today on how protein regulation in bacteria can actually lead to antagonistic drug interactions.  Counterintuitively, treating a bacterial infection with two different antibiotics can often increase the rate of bacterial growth, and his work helps to explain the mechanisms behind this seemingly paradoxical interaction. 

Essentially, it all boils down to the fact that cells need nutrients - and that wasting the nutrients instead of using them to promote cellular growth is a surefire way to ensure that they will die.  Some antibiotics (the ones that we will be talking about here) alter some cellular processes in order to force the cell to "waste" its nutrients.  One class inhibits transcription (the process by which mRNA is made from a DNA template so that it can then be made into proteins by the ribosomes).  Since there are still lots of ribosomes sitting around, they use up all the nutrients waiting to convert mRNA into protein, even though the antibiotic has essentially shut down mRNA production.  The second class of drug inhibits the production of ribosomes - but since mRNA production is still going at full speed, the mRNA's sit around unused - and making mRNA's then eats up all of the cellular nutrients. 

When these two classes of antibiotics are combined, they lead to a synergistic effect - since both mRNA transcription and ribosome production are inhibited, the cell no longer "wastes" nutrients, i.e., there is no longer an imbalance between cellular ribosomal and mRNA levels.  What this means for treatment is that if both drugs are used simultaneously, a higher concentration of each must be given than if both were used alone.  Since antibiotics are often toxic, this treatment plan is not always desireable - but it has the advantage of helping to prevent drug-resistant bacterial strains from forming.

However, the really cool thing about this mechanism is that it's built into most bacterial cells - but not for this purpose.  When bacteria encounter new environments, they often have to adjust their gene expression to account for new nutrient leves, as expressing too many genes in low nutrient conditions will lead to cell death, and expressing too few genes in high nutrient conditions will lead to suboptimal cellular growth.  Since bacteria can regulate this function naturally, the antibiotics just hijack the process, and hijacking both natural processes can negate the effect.

Overall, it was a very interesting talk, but the speaker is a physicist by training, and it showed in his preference for equations and mathematical models (which went just a bit over my head) over mechanistic explanations, which I would have preferred.  Still, talks like this one are a big part of why I like working at the MPI so much - an institute this big manages to have an interesting seminar like this at least once a week.  

Even though the cold weather decided not to play along, the City of Marburg put on their spring festival over the weekend.  As part of the proceedings, there was a free concert by a (very German) Beatles cover band, "The ReBeatles" on Saturday night.  If you ignored the slight accent, they were pretty good.  Their playlist focused mostly on the early (and in my opinion, worse) material, and Erica and I were by far the youngest members in attendence.  I have never seen so many older Germans start to dance/sway/generally make me uncomfortable after enjoying their Glühwein (not just for Christmas it would seem) in my life.  The concert, however, was not the main draw of the weekend - that would be the fact that the stores were legally allowed to open on Sunday, so a lot of people came in for the weekend shopping. 

Now you might be thinking why stores being open on a Sunday would be so special, but in Germany they are legally mandated to close in order to protect small businesses - the logic being that larger stores have more employees, so it is much easier for them to use this manpower to outcompete their smaller neighbors.  All it really means is that if you forgot to buy groceries on Saturday, you're SOL.  One nice side effect is that most of the downtowns are pretty empty on Sunday mornings/early afternoons, so it's a nice time to go for a walk/take pictures.  But back to the main story.

In addition to the free concert, the town put together quite a few events (moving brass bands, "comedians", and magicians) for the Sunday shoppers.  Since the Brothers Grimm taught at the University of Marburg for a bit (before being kicked out for being too liberal) and even collected many of their stories here, the town put up some small statues on storefronts and in the river with characters from the fairy tales - the most memorable being the over sized rear end of a donkey which was expelling gold coins.  Individual businesses were also allowed to organize their own events, which were mostly limited to 10%-off sales (try not to get too excited...) but a bike store in Weidenhausen (a district dating back to the 1500's) put on a bike market where I finally managed to pick up a used bike.  Throw in a few sausage stands, a crepe stand or two, and the spring festival turned out to be a very pleasant way to kill the afternoon and a good way to end the weekend. 

Yesterday the University of Marburg awarded the first ever Richard Hamann Prize for Art History to Professor Horst Bredekamp, who teaches art history at the Humboldt University of Berlin.  I found out about the award somewhat by chance, and decided to attend.  The ceremony took place in the main lecture hall of the "Old University" - a 19th Century neo-gothic reconstruction of a 13th Century monastery torn down during the reformation by angry protestants.  The lecture hall was quite impressive - neo-Romantic wall panels depict the (not always revolutionary) history of Marburg, with the main center panel given over to the Marburg Colloquy, as well as a very ornate ceiling.  Attending the lecture was worth it just for a look inside this room (and the free champagne at the end).

The ceremony opened with a short, generic introduction by Professor Volker Nienhaus, the President of the University.  It was fairly prosaic and just thanked everyone involved, especially the sponsors of the award - Herr and Frau Ahrens, who started the department store of the same name.  As the sponsor, Herr Ahrens was allowed to speak next.  He started off with the rather frank admission that he "...knew nothing about art history" and it went downhill from there.  By the end of it he was comparing himself to the art patrons of the rennaisance and stating that without the support of businessmen who "enjoy and consume art" then many of the world's great works would not have been produced.  To top it all off, for his conclusion he claimed that a department store and a theater were essentially the same, with the prime difference being, "A department store does not sell subscriptions - we have to work harder to sell our wares."  His monotone and plodding delivery didn't help matters much.

Next up was Professor Gerhard Wolf, the Director of the Max Planck Institute for Art History in Florence, Italy.  I didn't really have the background to understand most of his talk, but his animated manner made up for it.  Certainly a nice change from the previous speech.  His speech was followed by a piano interlude which was too self-consciously modern for my tastes - it kept going from rapid trilling in the treble register to slow plodding chords in the bass register, complete with unnecessarily long rests.

After this buildup, the honoree, Professor Horst Bredekamp came up to accept his award.  His speech was fantastic - it's clear that he is extremely passionate about his subject, and he presented his work with enough general detail that I was able to follow most of it.  Essentially, his theory is that pictures (any artwork that is not music) have a life in and of themselves.  At first I thought that he was speaking figuratively, but what he seems to have meant is that the artwork itself is more important than then the motivation that went into the art, i.e., the picture can take on a life of its own.  There were enough examples (he managed to connect Van Eyck with a modern French surrealist) for him to make his point somewhat convincingly, and he is also credited with helping to advance scientific theories of neurological recognition.  He was very gracious throughout, and even found some kind words to say about Herr Ahrens and his speech.  All in all, a very enjoyable evening and a nice change of pace from lab work.

Today I finally finished all of my courses for the winter semester at the Philipps-Universität Marburg and received my first "Scheins" - graded certificates of completion.  The transcript system here is very odd - nothing is centralized, so I now have to take these Scheins (properly stamped, verified, and signed, this being Germany) to the transcript office, where they will turn these Scheins into a transcript.  It's all more complicated than it needs to be, but now I know how the system works so it will be easier next time.   

Overall, I enjoyed the experience and got to take two interesting classes, "Special Topics in Infection Biology: Parasitology, Virology, and Immunology" (my favorite of the two, far and away) and "The German Regional Dialects" (which ended being fairly dry).  I came in prepared for a lot of work, as I'd heard that the German system was much harder, but found that "much harder" really meant "there is no homework so you read a lot on your own" - a system that I am completely OK with.  This system made it much easier to focus on the parts of the course that you enjoyed, while not spending too much time on what you weren't interested in, which I think helps promote a genuine interest in the field. 

The biggest surprise was my fellow students.  They were much, *ahem*, less-motivated than their American counterparts and seemed to do only what was necessary to scrape by.  The German grading system is somewhat stricter, in that their version of a "C" actually means average, but I found that I could put in less work than I had to at Pomona and still do well.  Part of this lack of motivation may be due to the fact that higher education in Germany is essentially free - my total bill for tuition and fees will run right at $500 for the entire year.  The professors have been great though, and I learned a lot - I was very grateful to be able to focus on one or two classes and learn at my own pace rather than simply study for a test.  Based on this semester, I'm looking forward to the next semester (which starts in April), where I'll plan to take some more sciences classes (immunology and microbial ecology) as well as another language (suggestions?  Right now I'm thinking Arabic, Spanish, Russian, or Dutch) and course to help better my German accent. 

The University of Michigan, School of Public Health.  Making this decision turned out to be much tougher than I had anticipated - I did not expect to receive an admissions offer from so many schools!  In the end, the combination of great value (even with 10k a year from Columbia it would have been 20k more expensive per year - and a name is not worth that) and the excellent program (their international epidemiology is one of the first and the best) sealed the deal.  The connection with the CDC at Emory was tempting, but their international options weren't as appealing - the University of Michigan had a much greater variety, and research will be easier to get involved in there. 

So now one major question remains:  can I survive the deathly cold winters of central Michigan?  I guess that we'll just have to wait and see.

More good news on the admissions front:  the Mailman School of Public Health offered me a partial tuition scholarship ($5000 per term)!  I'm kind of torn - even with the scholarship, the University of Michigan will still be cheaper.  However, I also have bad news - the Rollins School of Public Health at Emory did not offer me any merit-based aid, so it looks like they are out of the picture.  The University of Washington also drags behind, as I can't even get a response from their professors regarding funding.  So on the plus side, I finally have all the info that I need to make my decision, which will be coming soon.  

Today was the fourth and final day of the Fulbright Conference, and it was a fairly laid-back one.  Like every day this week, I started off with a free breakfast in the hotel lobby, then went off with another Fulbrighter (engineer working with Deutsche Bahn in Munich) to go see the Memorial to the Murdered Jews of Europe.  The monument itself is very simple - 2,711 granite slabs of varying heights arranged in a grid.  It's not symbolic of anything and was designed to let the visitor wander through, get disoriented (navigation is easy, but the grid is small enough and the steles high enough that you'll get lost from traveling companions quickly and run into them when you least expect it), and ponder the tragedy of the holocaust.  It was very moving, especially the museum below it, but I did not like that it focused only on the Jewish victims of the holocaust.  Don't get me wrong, they should have a monument - as should the other major ethnic groups that were victims - but I think that it is unfair to the memory of the other groups that also suffered to be excluded from Berlin's main memorial. 

From there I walked along the western side of what used to be the Berlin Wall (and is now a major street) to the Reichstag, where I met Erica and her family (after stopping to get coffee on the way).  From here we walked through the Tiergarten (the major park in the center of Berlin, which has more green space as a percentage of area than any other European capital), also known as Berlin's green lung (more brown this time of year, but meh) to the Museum of Musical Instruments - which was surprisingly fascinating.  They had a nice collection of pianos, harpsichords, and organs, some with incredible levels of detail and artistry.  We spent about an hour there, then walked under Potsdamer Platz, the central square of West Berlin, and the difference with the East was amazing.  The former east is still full of Soviet-era pre-fab, and the main square, Alexander Platz (where my hotel is) is surrounded by low-slung cement monsters.  In the west, Potsdamer Platz is now home to an airy covered park surrounded (fairly closely) by shopping malls of steel and glass.  Continuing the walk, we went past Gendarmenmarkt, a very nice square with two cathedrals and a theatre house.  From here I went back to the hotel alone to attend a seminar put on by Fulbright.

The seminar was (nominally) about the effect of Obama on the German political landscape, and Dr. Constanze Stelzenmüller, the former editor of Die Welt (think The Economist in Germany), was one of the highlights.  Her opinions were very pragmatic - attempt to encourage democracy in Eastern Europe while keeping Russia at bay, work with the US but not for the US, and to take a cautious tone with Obama from the start.  She did anticipate better relations and more productive foreign policy, but also expressed the idea that in the current financial crisis, economic policy will become foreign policy.  This talk was easily the best one that Fulbright put on this week - questions asked by the audience were actually answered directly - and without political juggling.

After the talk I was worn out, so I went up to my room to relax for a bit and read, enjoying the view at sunset out over Berlin from my hotel window.  The Fulbright Committee put on a nice farewell dinner for us in the hotel, and I got to talk with other Fulbrighters about their projects.  Thankfully, I'm not the only one whose project isn't moving as quickly as they had planned, so it was good to commiserate about the same frustrations.  After dinner I went over to meet Erica and her family again and hung out with them for a while.  From there I walked back to my hotel so that I could enjoy Berlin at night one final time. 

The Fulbright Conference continued on Tuesday, kicking off with some project presentations by other Fulbrighters from around Europe.  These projects ran from the extremely fuzzy (teaching middle school German children ethnic dance to combat racial stereotypes - but only 6 times) to the very technical (Photoionization of Highly Charged Ions in an Electron Beam Trap utilizing Advanced Synchrotron Radiation Sources) and everything in between (Renewable Energy Policy).  In general, they were pretty interesting, and the 5-minute was a nice balance.  Following these talks, we had a short break and then were welcomed by Barbara Kisseler, the Head of the Senate Chancellery of Berlin (President of Berlin Senate, Berlin is a city-state) where we learned about why Berlin is such a great city.  Although 60 billion dollars in debt, they plan to spend 400 million of their 640 million share of the bailout package on culture, as they think that culture is what draws people to Berlin and they hope to make more money off of it.  For a politician, she gave a nice speech, but the highlight of these events was the location - inside Berlin's town hall and in the very room where the Berlin Congress took place. 

After the speech we got a quick lunch, and from there I went to go meet Erica's family for a walking tour through the old part of the city.  The walking tour was much better than the bus tour, and the sunny weather (I forgot that they were allowed to have such weather in Germany) was a nice change.  We spent most of our time inside the Berlin Cathedral, originally built in 1902 to show off the wealth of the German Kaisers.  Surprisingly, the cathedral was protestant, and it had a nice outdoor balcony that you could walk around to get some good views of the city. 

After the cathedral we took a walk up to Prenzlauer Berg, a formerly up-and-coming neighborhood that has now arrived.  It was a little bit too self-consciously trendy for my tastes, but like the rest of Berlin the streets were nice and wide - for such a huge city, it's fairly walkable.  A lot of this walkability stems from the fact that until the Prussians moved their capital here, Berlin was mostly a grouping of small towns.  With the arrival of the Prussian court, the towns just kept expanding until they all touched.  Unlike LA, each district maintains a unique feel and a sense of identity, and the cultural scene will shift from one district to another.  Anyways, after a short trip through there, we reached a nice neighborhood restaurant, where we had some good schnitzel and a few locally-brewed beers. 

From there we took the U-Bahn (subway) back to their apartment and talked for a bit.  I left around 9:15 and made my way to the Reichstag, the roof of which remains open to the public until 10:00, but once you get up they don't make you leave until midnight.  After about 10:15 I had the dome and roof pretty much to myself, and got to enjoy it at my leisure.  The design is quite striking - a glass dome overlooking the floor of the German Bundestag (House of Representatives), which serves three functions:  providing light (through 360 mirrors on a central column), climate control (cools in summer, warms in winter through heat transfer and insulation), and finally as a symbol for the new transparency of the German government following the war.  The Reichstag was never used during the Nazi administration, so it's one of the few buildings free of the associative guilt.

For me, the dome symbolizes a more modern Germany.  It's open, has a forward-thinking and beautiful design, is a little bit sterile but has some unique character, and helps promote ecological stability.  Being up alone on the roof was an amazing experience:  I had been up there before, but only during the day, and it was just too crowded for my tastes.  At night it was a completely different feeling:  the solitude makes it much easier to reflect on the history and symbolism of the glass cupola, and Berlin looks great at night.  It's a nice flat city, with only a few skyscrapers.  The rest of the towers belong to churches, palaces, and other historic buildings, while it spreads far enough out that there's still a significant big-city feel.  Needless to say, should you find yourself in Berlin, go at night.

After the Reichstag I walked back to the Brandenburg Gate (also deserted), passing over the site of the former Berlin Wall, marked by cobblestones in the street and now crossed daily by hundreds of cars and pedestrians.  Along the way are memorials to those killed trying to cross.  Again, this experience was very Berlin; no other city I've been too keeps modernity and tragic history in such close proximity to each other, managing to embrace both, taking hope in the former and reflecting on the latter.  Sometimes the rebuilding goes a bit too far and the history can get lost, but all things considered, Berlin manages to pull off both. 

The day started off with a panel discussion about the future of Germany and how it has coped with the challenges of the reunion.  I was looking forward to it, as the Fulbright Commission had managed to get a former head of the German Green Party, the political editor of Die Welt, a respected German newspaper, and the director of the American Institute for Contemporary German studies.  Sadly, the former head of the Green Party destroyed my hopes - he was a giant windbag, and everything he said sounded like it came straight out of a (bad) political speech.  Most of his answers focused on why his decisions were the right ones, and after a 5 minute introduction got lost in a sea of conclusions and mixed metaphors.  He even said that "We didn't want [The US] to think that we were trying to start the 4th Reich" at some point, and then went on to claim the Neo-Nazi party, NPD, is not really a problem.  Well and good, but they won 25% of the vote in some districts (thankfully not many, but it's still enough to be a problem).  He's running for the European Parliament, so I hope that he loses.  The other speakers were much better - brief, insightful, and funny, but they often didn't even get the chance to speak.

After that nonsense I need a break, and went to the Pergamon Museum with Samuel, another Fulbrighter also studying in Marburg.  This museum was simply astounding - each new room had a facade of a ruined temple, an altar (like a reconstruction of the Pergamon Altar), or, my favorite, the Ishtar Gate.  This gate might not sound all that exciting to you, but I've been reading about it since I was 8 - and every picture I saw of it was captioned with "Courtesy of the Vorderasiatische Museum, Berlin" so I've been looking forward to seeing this for a while.  Originally the main entrance off the Processional Way coming into the city of Babylon, it was one of the main reasons why the walls of Babylon, and not it's Hanging Gardens, were considered to be a Wonder of the World (back in the day and such).  The reconstruction is gorgeous, and it's hard not to be awestruck. 

After the museum I tagged back to the hotel quick, then it was off to the Haus der Kulturen der Welt for speeches (including an excellent one on the different geopolitical goals of Europe and the US by Dr. Klaus von Dohnanyi), music, and free food (and an adult beverage or two).  Following this nice opening ceremony (we'll pretend and forget that we all didn't arrive yesterday) I met up with Erica and her family, and we took a short walk through Berlin at night to finish the day off. 

So I should probably explain what I'm doing in Berlin, as a starter.  The German Fulbright Commission puts on a conference for all German Fulbrighters here every year, but since this year is the 20th Anniversary of the fall of the Berlin Wall and the 60th Anniversary of the founding of the German state, they went all out and invited all Fulbrighters in Europe and all Germans going to America.  So in total, there's about 600 of us, and they put us up in a nice hotel (well, large and clean) looking over the city - especially the historic center and the west. 

Picking up from where the London post left off...  after leaving the hotel, I walked around Alexander Platz for a bit before heading off to my tour, which was "Berlin Mitte - Architecture and Churches." Normally this would be right up my alley, but when I showed up I saw a bus.  I hoped that the bus would take us to a more central location before dropping us off to do a walking tour, but sadly it did not, and we just drove around the city looking out the window.  This tour confirmed why I hated this approach to sightseeing - you miss a lot of the detail and at the end of the day you have no real idea of where you've been or where anything is in relation to the other attractions.  Other than that, the tour was fine - general tourist information punctuated by an interesting visit to Germany's Tomb of the Unknown Soldier (I use this term, but concentration camp victims and victims of totalinarian regimes are honored equally) with a haunting interpretation of the Pieta by Kathe Kolwitz.  After this stop we headed over to the new synagouge, which I loved - the style is very moorish and it almost looks out of place next to the staid Wilhemine buildings surrounding it. 

The tour also opened my eyes to the extreme war damage that Berlin suffered - over 65% of the old city was destroyed, and since people needed housing, concrete pre-fab (especially in the East, which contained most of the historic buildings) still dominate the landscape.  But recently the modern has begun to mix with tradition, usually to great effect - IM Pei designed the addition to the German History museum, and this wing adds a refreshing touch to the city's architecture (the new governmental offices are strikingly modern, full of glass and metal, resulting in a very open feeling).  After this bus tour we headed over to a restaurant/pub where we had our introductory dinner and a reception.  We stayed here for a bit (with free beer, how could you not?) and then walked our way back to the hotel.  Thankfully, the weather was nice, and it gave me a great chance to see some parts of Berlin by night.