Showing posts with label research. Show all posts
Showing posts with label research. Show all posts

Wednesday, September 07, 2016

a fond farewell

Rainer Jaenicke 1930-2016

My old professor or Doktorvater, as we like to call PhD supervisors in Germany once the title is in the bag, died at the end of July aged 85. Throughout our shared project (one year final year thesis plus three years doctoral thesis) he was a generous friend more than a boss, and remained one in the 23 years after. So, I’ll try to honour him with an obituary, which is not a format I have often had to write, but as time goes on, one does tend to have more farewells to make. Here’s my first attempt, I may add to it later.

Rainer Jaenicke was the youngest of the four children of a semi-famous chemist, Johannes Jaenicke (1888-1984), who during the Weimar Republic was the assistant of Nobel Laureate Fritz Haber, assisting, among other projects, with the doomed attempt to isolate gold from sea water to pay off Germany’s debt, and his wife Erna Buttermilch (1895-1961).

Johannes Jaenicke spent much of his long life meticulously compiling material for a biography of the great chemist and controversial figure (Haber’s ammonia synthesis process produces half the nitrogen contained in the bodies of the world population, but he also pioneered the use of chemical weapons), but, as he lost his eyesight with age, he ended up being unable to write it. All existing biographies of Haber are based on Johannes Jaenicke’s extensive collection, which has been archived by the Max Planck Society.

His three sons all became professors of some kind of chemistry. Walther Jaenicke (1921-2011) of physical chemistry at the University of Erlangen-Nürnberg; Lothar Jaenicke (1923-2015) of biochemistry at Cologne, and Rainer Jaenicke of biophysical chemistry at Regensburg.

The one thing I know about Rainer Jaenicke’s childhood in Frankfurt is that at age 13, he teamed up with a young pianist who accompanied his flute playing, Agathe Calvelli-Adorno. They lived happily ever after, as they say, and played music together for over 70 years.

Both families had partial Jewish background and suffered for it during the Nazi time, but made it through. Her Jewish grandmother was deported to concentration camp Theresienstadt and died soon after liberation. The Jaenicke brothers saw their career options limited by being fractionally Jewish according to the Nazi arithmetics (through their mother) but made up for it after the end of the “1000 years”.

Rainer Jaenicke married his pianist just before he obtained his PhD in physical chemistry with Hermann Hartmann (1914-1984) in Frankfurt, started a family, and got his Habilitation in 1963. With their children, they set off to Pittsburgh, Pennsylvania, where he worked with Max Lauffer (1914-2012) until 1969. Soon after his return he secured a professorship at the newly founded University of Regensburg, Bavaria. He took the chair for biophysical chemistry, which he held until his retirement in 1999. I believe he also served on the committee that commissioned / chose the around 30 major artworks that are scattered around the campus. For a project of this size it was a legal obligation to have a certain amount of “Kunst am Bau”, and there is a nice little book, called “Rund um die Kugel,” discussing all the artworks.

From the US, he brought back the research interest of protein assembly systems such as tobacco mosaic virus (TMV) – a classical system to study self-assembly which in my student days was still used in the practical biochemistry course in his department. From there, his research interests widened to protein folding and stability, including stability under extreme physical conditions like salinity, high and low temperatures and high pressures, which is where my thesis happened.

By the 1990s, one of his trademarks was to keep old-fashioned physical methods of analysis alive, especially analytical ultracentrifugation. This method involves spinning a sample so fast (40,000 rpm would be a typical speed) that large molecules such as proteins are gradually pulled out of solution by the centrifugal force. And this happens in a transparent cell, such that one can shine light through the sample and actually watch the molecules go down.

During my time in the lab (1989-1993) he kept two Beckman model E centrifuges alive and spinning, which was an achievement in itself, as the company had stopped making and indeed servicing these instruments, each the size of a generously-proportioned wardrobe, some time in the 1980s. Several dead machines in the basement were cannibalised for spares. As he was reluctant to persuade students to dedicate three or four years of their lives to an extinct technology, he did many of the centrifugation runs himself, and had great fun fiddling around with the machines.

And right he was too, because around that time, Beckman changed their mind and decided to develop a new instrument from scratch. I vividly remember Howard Schachman (1918-2016 - he died a week after RJ) visiting the lab, another model E aficionado, recalling how the company asked him for advice. As they had closed down the relevant department many years ago and fired everybody who knew anything about analytical ultracentrifuges, they were facing an uphill struggle trying to build a new one. But they got there in the end, and the instruments are now a bit more compact, so they can sit on a lab bench and feed their results to a computer.

As a supervisor, he was very generous with ideas, suggestions and help in establishing collaboration opportunities. I had collaborations with five labs outside Regensburg, four of which he enabled with phone calls to the relevant group leaders (the fifth was someone I met at a conference). While always ready to offer this kind of help and support, he never ever told me what to do – I had a rather painful awakening when I moved on to a postdoctoral fellowship in the UK and lost some 95% of the freedom I had been used to.

Part of the reason for my freedom was in the fact that during my doctoral thesis I was the only person in the lab working on the effects of high hydrostatic pressure. There were crowds of protein folding people and of those doing thermal stability, a few looking at salinity. Thus, there was no need for higher level co-ordination, there was no risk of my work overlapping anybody else’s, and I could basically do whatever I wanted. In this situation, as my own sub-group leader, and as I was also writing my own papers from day one, I put the asterisk indicating the correspondence author behind my name, just on the naïve assumption that he wouldn’t want to be troubled with the paperwork. He never queried that – only when we wrote a review together after I left the lab did he regain the asterisk, which any other professor would have claimed as their statutory right throughout.

Incidentally, he didn’t try to steer his children into a certain direction either. His daughter became a nurse, his sons an actor and an artist. He always highlighted their career choices – very unusual for a family of chemists – with pride, contrasting them to the children of colleagues (presumably including, though not mentioning, his brother) who were groomed to follow in the scientific tradition.

During my Regensburg years, I gained the impression that he had never really adapted to the Bavarian temperament of the people around him. Regensburg being a modern university serving a regional constituency (as opposed to the ancient universities like Heidelberg which attract students from all of Germany and indeed abroad), even most of the faculty colleagues had a conspicuous regional accent - not just in their language but also in their thinking and (conservative) worldview. He probably found he had more in common with the many international visitors he invited to Regensburg than with his immediate colleagues and next-door neighbours.

Thus, even though regulations for professors of his generation would have enabled him to use university facilities as an emeritus indefinitely, it was no big surprise to hear that in the late 1990s, after retiring at 68, he moved to the small town of Schwalbach am Taunus, within S-Bahn commuting distance of the city of Frankfurt, which he routinely referred to as home. The couple bought a bungalow – modest looking on the ground floor, but with a basement doubling the area and providing an impressive exhibition space for works of their artist son, Alexander Calvelli, as well as other graphic works which they collected. There were also guest rooms complete with musical instruments – visitors had the choice of sleeping in the presence of a harpsichord or a grand piano.

For nearly two decades, they kept a busy social and musical life at Schwalbach. The last time I visited, in the spring of 2014, the onset of memory loss was noticeable, although he could still play music. His condition gradually worsened to cut him off from the outside world, with the impressions from music remaining the last connection.

some items from my collection of RJ memorabilia ...

Tuesday, May 22, 2012

amyloid and Alzheimer's disease

Back in the late 90s, I was working with some model peptides which I had designed for use in studies of nascent protein folding, but they kept aggregating. Chris Dobson suggested to check whether the aggregates had the hallmark featres of amyloid, and indeed they had, so I slipped into the study of amyloid, which is the kind of tangled protein aggregate one finds in Alzheimer's disease, BSE, and Parkinson's. Quite a few others did at the time, as many proteins and peptides had the ability to form these structures, even if their native states had no disease association whatsoever.

I haven't done much about amyloid since publishing my last research papers, but recently spotted a few papers that looked promising both for the understanding of amyloid formation and for the treatment of Alzheimer's disease, so I wrote a feature about these things, which is out in Current Biology today.

Understanding amyloid and Alzheimer's disease

Current Biology, Volume 22, Issue 10, R381-R384, 22 May 2012

doi:10.1016/j.cub.2012.05.006

html text

PDF file

(NB: my features remain on free access only until the next issue appears, i.e. normally 2 weeks, sometimes 3, and they return to free access a year after publication)

Alois Alzheimer (1864-1915)

(Wikipedia)

Wednesday, August 04, 2010

how alpha turns into beta

(plus breaking news on gamers predicting protein structures, below)

Ten years ago, I published a review on alpha helical proteins converting to beta sheet structure, which may happen, for instance, when proteins “misfold” to form amyloid fibrils similar to the ones observed in a range of diseases including Alzheimer’s (1). I had studied amyloid formation in peptides for a few years, and my main interest in the alpha/beta conversion was the fact that it violates a central dogma of molecular biology, namely that each polypeptide sequence defines only one stable native structure.

Zhao Qin and Markus Buehler at MIT have now published molecular dynamics simulations showing in detail how the conversion from alpha to beta may happen and how it changes the properties of the polypeptide chain in distinct phases (2). While I’m not really in a position to give expert judgment on MD work, I think the alpha to beta transition has become quite important in recent years, due to the wide range of medical conditions involving amyloid, but also based on interest from the material sciences, so I reckon it will be useful for the people still in the field to have these mechanistical insights into how proteins change shape.

References:

1) M. Groß, Current Protein and Peptide Science 2000, 1, 339-347
Proteins that convert from alpha helix to beta sheet: Implications for folding and disease
2) Z. Qin, M. J. Buehler, Phys Rev Lett 2010, 104, 198304
Molecular dynamics simulation of the alpha-helix to beta-sheet transition in coiled protein filaments: evidence for a critical filament scale


I've used this picture before, but I just can't get enough of it:





----------------
Breaking news, added at 1800 h London time :

Gamers can predict protein structures

In other protein folding news, a paper out in tomorrow’s issue of Nature (p756) tackles the notorious “folding problem” , i.e. the fact that it is still hard to predict the 3D structure of an unknown protein from its linear amino acid sequence, by handing it out to volunteer gamers. The combined efforts of tens of thousands of players of a multiplayer online game yielded a rich, new set of search strategies for the prediction of protein structures, the Nature press release says.
Seth Cooper and colleagues have developed a multiplayer online game called ’Foldit’, in which incorrectly folded protein structures are presented as puzzles. The players, many of whom do not have any formal scientific training, manipulate the protein structures to optimize the computed energy.

The researchers used ten puzzles, where the target protein structures were not publicly available, to test the players’ abilities: they found that players outperformed the ‘Rosetta’ structure prediction software on five of the puzzles. Many players worked collaboratively and — unlike computational approaches — they explored not only conformational space but also the space of possible search strategies.

The authors believe that further analysis of the strategies used by the top-ranked Foldit players could lead to improved automated algorithms for protein structure prediction and could facilitate research on related problems, such as protein design, that rely on computational algorithms.

Nature video

my article in German about the FoldIt program, Spektrum der Wissenschaft 10/2010

Saturday, December 26, 2009

crunching numbers

One of my xmas holiday traditions is that I check the science citation index to see whether anybody has bothered citing my old research papers. This year, my five earliest works have gone empty-handed, but most others have still received a fair number of citations. The top three in new citations are:

1. my proteins and pressure review, which is also at the top of the overall citation list (updated version now online).

2. Jaikaran et al. J. Mol. Biol. -- an amyloid paper that has risen steeply to no. 4 of my ranking and will probably reach no. 3 next year. From the same project comes:

3. Higham et al. FEBS Lett. (climbing to No. 9). Very pleased to see the amyloid papers are still finding attention. My own role in these was only a minor one, but the first authors definitely deserve the recognition.

My Hirsch index (number n of citations that have been cited at least n times) is stuck at 16 now, which is a shame. For six years after retiring from research I watched in amazement as it kept climbing without any input from me.

Anyhow. Always fun to do some statistics. More about this next year.

Thursday, February 26, 2009

current protein and peptide science

In the old days, I used to be on the advisory board of the Journal

Current Protein and Peptide Science

and I also contributed two reviews to it. However, I never managed to get my access to the online journal working, so I am very pleased that I have now, at last, received pdf files of my reviews:

Groß M (2000): Current Protein and Peptide Science 1, 339-347
Proteins that convert from alpha helix to beta sheet: Implications for folding and disease

Gross M (2004): Current Protein and Peptide Science 5, No. 4, 213-223
Emergency services: An bird's eye perspective on the many different functions of stress proteins

They may be a bit dusty by now, but if anyone is still interested, I'll be happy to send the pdfs.

Thursday, January 15, 2009

reasons to be symmetrical

Given that proteins are fundamentally asymmetric (their chain has a unique directionality, and most of the chain links have a handedness), it may seem surprising that a majority of natural proteins forms highly symmetrical complexes involving two or more protein subunits.

In a "dispatch" in the current issue of Current Biology, Kevin Plaxco and I have commented on recent work that manages to explain this natural tendency towards symmetry at least for dimers:

Protein Complexes: The Evolution of Symmetry
Current Biology, Volume 19, Issue 1, R25-R26, 13 January 2009
(summary is free, access to pdf requires subscription or institutional access)

Monday, December 29, 2008

summing up

one of my end-of-year rituals is checking the citation counts of my papers, and as in previous years I have been pleasantly surprised to see that all but two (no.2,3) of the 18 papers listed here have acquired new citations this year. Even the earliest one, which is now 18 years old !

New on the list is the review:
Groß M (2000)
Current Protein and Peptide Science 1, 339-347
Proteins that convert from alpha helix to beta sheet: Implications for folding and disease
10 (9;6;5)

which has been a bit of a sleeper but may still rise to fame ...

Tuesday, July 01, 2008

protein shapeshifter

There is an intriguing "perspective" in the current issue of science magazine (p.1725) about proteins that can adopt different folded conformations under different conditions.

The most interesting new example is Lymphotactin, which can form a monomer with alpha/beta structure, or a dimer with no alpha helical content at all. This is published in PNAS, 105, 5057, 2008.

Way back when I have also written about proteins switching between alpha and beta structure, mainly in the context of amyloid formation by alpha helical proteins:

Groß M (2000): Current Protein and Peptide Science 1, 339-347
Proteins that convert from alpha helix to beta sheet: Implications for folding and disease


But as I never got round to learning Greek, I didn't think of calling them "metamorphic proteins" as the Science piece now does. Damn. Another missed opportunity ...

Wednesday, December 19, 2007

counting citations

Once a year, typically around this time, I visit the science citation index to check up on my old research papers. So here is my updated list of citations. I have to say I'm really chuffed to see that people still cite nearly half of the papers, even though I haven't been involved with any of this stuff for almost 8 years. So I'm not travelling around the conferences to blow my own trumpet and all that. Considering they are out there on their own, the papers are managing quite well, I think.

PS I don't include the books in the stats, but they too get cited every once in a while.

Thursday, October 04, 2007

hirsch index

The Hirsch index is increasingly being used to compare research achievements, and it has been reported in Nature and discussed in the correspondence pages of Nature and the Nautilus blog.

Essentially, h is the number of papers that somebody has published that have been cited at least h times. So if you have a ranking of papers by citation numbers, you go down the list, rank number increases while citation number decreases. The last rank number which is equal to or smaller than the corresponding citation number is the h index.

I'm all in favour of the h-index as it has rewarded me
for doing nothing. I left research in 2000, when my
h-index (determined retrospectively) stood at 10.
Since then it has increased by one unit every year
without any input from me (not even self-citations)
and it is now 16, as you can see here.

But I think people whose career prospects depend on this kind of measure, should think very carefully about this ...