Reactions – Francesco Stellacci

1. What made you want to be a chemist?

In reality I am a materials scientist, chemists are my ‘cousins’. I chose to become a materials scientist because I could not decide between physics and chemistry, and materials science seemed a good compromise. I am still truly happy for that choice even though as my career has progressed I have drifted more and more towards chemistry.

2. If you weren’t a chemist and could do any other job, what would it be – and why?

Well, I chose science because I felt (and keep feeling) that it was a way to help people around me and develop knowledge that would eventually lead to improved living conditions for everybody. This dream keeps driving me everyday and I would not exchange it for anything else. So if I could not be a scientist I would probably like to be a politician, with the exact same spirit. On the other hand, an old dream of mine is that of being a photographer, one that tells the world with an artistic touch like Henry Cartier-Bresson.

3. How can chemists best contribute to the world at large?

Well, we can all use our talents to improve the way we live in this world, using less and less of its resources and we could all mitigate the toughness that illness and pain bring to life. A far dream is to use science to limit the divide between rich and poor countries. In a world in which technology is evenly distributed the difference due to uneven access to natural resources (like water) would be mitigated (I think…).

4. Which historical figure would you most like to have dinner with – and why?

Hum, this is a tough one, do soccer players count? Just kidding…I would definitively like to have dinner with the ones that changed the world when others did not see the need for it. And they did it for the better, with love. So Saint Francis of Assisi and Gandhi would top my list. But if it is only one dinner (too short to exhaust all of my questions…) why not Cleopatra? Just kidding again…

5. When was the last time you did an experiment in the lab – and what was it?

A serious one? I don’t recall…Very, very sad!!! I don’t even remember what my last experiment as a post-doc was. I should, it would be equivalent to the last kiss to a loved one! I do many experiments because I teach a lab class, so the last one would be measuring the size of polymer coils in dilute solutions with DLS. Nothing like the thrill of a true research-oriented experiment.

6. If exiled on a desert island, what one book and one CD would you take with you?

The book would be something I have not fully read but always wanted to finish reading, so the Divina Commedia (Holy Comedy) by Dante Alighieri. The CD would be a Pink Floyd one, really tough to pick one though, I love them all.

Francesco Stellacci is in the Department of Materials Science and Engineering at MIT and works on supramolecular materials science, in particular his interests are in the interactions that supramolecular assemblies of molecules have with the outside world when they have a specific nanostructure.

NChem Research Highlights: capsules, spectroscopy and nanomachines

Morning everyone, Friday can only mean one thing.

First up is a pretty clever idea: a supramolecular capsule with pores that can open and close. Some pretty obvious advantages for controlled release.

Next to be covered is a paper from Science that you might have seen highlighted elsewhere: a nifty spectroscopic technique where they vibrationally excite a molecule before studying its rotational spectrum. It’s so fast you can look at both isomers of a molecule – and all the states in between.

And finally, a polymer whose phase transition involves such a large change in length that a fibre is able to make an object 250 times its weight move on uphill. The object is a US dime, so there are potential uses in piggy banks across the world!

I hope you enjoy this week’s batch – time for me to edit next week’s…

Neil

Neil Withers (Associate Editor, Nature Chemistry)

Dodge this.

In case you somehow were not aware, we are in the midst of the (I think first ever?) World Science Festival. Yes – somewhere in New York City, people are discussing Einstein’s dreams, morality, and bioterrorism (not at the same time). If any of you are attending, let us know how it’s going. Along with this conference came the announcement of the first ever Kavli Prize recipients. Norway, apparently sick of being overshadowed by it’s eastern neighbor, is giving away it’s own million-dollar prizes in the modernized categories of neuroscience, astrophysics, and nanoscience (this last to Louis Brus and Sumio Iijima). Along the lines of my previous post, it will be interesting to see how prestigious these new awards will become, and/or whether (as Mitch commented) the work already speaks for itself.

Another event coming up soon, and related to whether or not science speaks for itself, is the release of the updated impact factors from ISI. There’s an interesting article in the latest C&E News about whether impact factors are useful/meaningful/accurate (which there’s always room to discuss), as well as a proposal for developing a new metric to gauge the ‘importance’ of a specific article, journal or researcher’s body of work. In general, it’s quite interesting, but there are several important factual errors. So, just in case these are wider misconceptions, let me clear a few things up:

1) The Nature ‘family’ of journals (Nature, and the research and review journals that have ‘Nature’ in their name) do not have editorial boards, or advisory boards; instead, the journals employ full-time, professional editors who are Ph.D. scientists drawn from relevant fields. [A quick correction 05/30: I’ve learned that the review journals do use advisory boards to help select research highlights.]

2) Our highest priority in considering and publishing new science is the quality of the work, not whether the topic is ‘hot’, or whether an author has published with the journal before.

3) While we welcome conversations and inquiries about upcoming manuscripts and ongoing research, ‘hammering’ on an editor (or similarly, overly aggressive comments to referees) is typically counterproductive.

Phew! That’s it.

In the end, perhaps Mitch is right, that a good paper is good no matter what, and that people find it and tell other people about it and eventually you can’t avoid reading it? Here’s hoping all our papers become ones you can’t help but love.

Catherine (associate editor, Nature Chemical Biology)

Reactions – Marty Burke

1. What made you want to be a chemist?

At first I was simply trying to impress Christina White, my organic teaching assistant when I was a freshmen in college. When I later realized the tremendous power of organic synthesis to promote the understanding and betterment of human health, I was hooked.

2. If you weren’t a chemist and could do any other job, what would it be – and why?

When I was a kid I dreamed of becoming a major league baseball player, but talent (or rather a lack thereof!) has a funny way of working these things out.

3. How can chemists best contribute to the world at large?

I always tell my students that when you learn how to make molecules you make yourself a very powerful person. It is truly staggering when you let your mind race about all of the important problems that ultimately represent challenges at the molecular level. I think the most impacting chemists tend to be those that identify an important molecular problem and then solve it. Interestingly, the problem identification may be the most critical part of this process.

4. Which historical figure would you most like to have dinner with – and why?

It’s tough to pick just one. I guess if I were forced to make a choice I would have to say Sir Isaac Newton – now that guy could pick a good problem!

5. When was the last time you did an experiment in the lab – and what was it?

I still try to work in lab as much as possible, but these days I usually just make starting materials for my students. This gives me the opportunity to stay involved without getting in the way of the students’ discovery process. This was one of the many very useful pieces of advice that I got from Scott Miller when I was preparing to launch my own group.

6. if exiled on a desert island, what one book and one CD would you take with you?

My favorite book is 100 Years of Solitude, and if I could only have one CD I would probably take the soundtrack from Garden State. But to be honest, if I were exiled on a desert island I would spend most of my time trying to get back!

Marty Burke is an assistant professor in the Department of Chemistry at the University of Illinois in Urbana-Champaign. His research focuses on the synthesis and study of small molecules with the capacity to perform higher-order, protein-like functions.

NChem Research Highlights: silenes, cortistatin and magnetic beads

Morning everyone, it’s research highlight time!

Apart from having a really cheesy headline(credit goes to Gav), my piece is on a double-whammy in silicon chemistry: the first compound with two C=Si double bonds AND the first metal-substituted silene — in the same compound.

Steve tackles some total synthesis, writing about Phil Baran‘s assault on (+)-cortistatin A, where they had to use a side door to access a ring-expanding cascade. There’s more about this over on Totally Synthetic.

And finally…how are your knees? If they’re suffering from osteoarthritis or acute pseudogout, chances are they’ve got crystals of calcium phosphate in them. Read Gav’s highlight about how the crystal culprits can be detected with magnetic beads.

Neil

Neil Withers (Associate Editor, Nature Chemistry)

JACS 2.0

I’m sure all you dilligent up-to-the-minute literature-lovers out there have just received your Journal of the American Society table of contents alert for issue 21. I trust you noticed the little ad for ‘JACS-β’ and the editorial

JACS has launched a beta website, which includes a ‘virtual thematic web issue’ (on total synthesis), downloadable PowerPoint slides of all the figures/schemes of an article and (gulp) “Listen to the complete text of selected JACS communications.” For real.

Personally, my favourite part is the ‘What kind of smartphone do you use?’ type of questionnaire along the RHS. Facebook-tastic!

A bit more seriously, it’s good to see JACS getting a bit 2.0 (or indeed 21st century) on us – everyone likes a theme issue now and then (although web-only means you don’t get a nice hard copy to refer to endlessly), and I bet a lot of lecturers will like the PowerPoint slides, but…podcasts of full-on research articles? I haven’t listened to one yet, but might save one for the commute soon – anyone else tuned in and care to let us know what they think?

Neil

Neil Withers (Associate Editor, Nature Chemistry)

The platypus as inspiration

Hi all,

Our June issue just went on line. I mean, just like 2 nanoseconds ago. This is brand new information, so hurry and go check it out. Among other goodies, you’ll find a proposal for the future of antibody technology, evidence for a global biosynthetic assembly line, and a beautiful tribute to a great scientist.

This issue is not just for you to sit back and admire, though. This month, we want to get your thoughts on the ways in which we can, do, and could communicate with each other. We also want to know how you integrate the web in your life, and we don’t mean between your toes. At our journal (and many others), the Correspondence section serves as an official venue for comments (and sometimes responses) on papers that we have published, as well as providing a forum for general conversations of interest to the community. In addition, in discussing specific papers, a growing number of journals like the PLOS fold and Biology Direct offer an opportunity to comment alongside the paper to raise technical or conceptual concerns, or theoretically to talk about new ideas raised by the article (my fairly minimal search turns up mostly the former, though). Faculty of 1000 also offers a forum for professors to highlight papers that they think their peers should be aware of. In regards to more informal topics, Nature Network has seen some great online discussions and happy hours, LinkedIn offers opportunities to establish a scientific network, and Nature Publishing Group is increasingly making a place for itself on spots like Second Life and Facebook. Similarly, the number of science blogs seems to have exploded in recent years, covering both scientific topics and things more related to being a scientist than the work itself.

With these growing online options, we are curious about how you all view the future of scientific communication. Here are a few of the things on our collective minds:

1. What should our Correspondence section include? Do you see a continuing need for this formal mechanism of communication?

2. What is the future of scientific correspondence more broadly? i.e., where do you go to find science news and cool papers, or to initiate or participate in discussions, and what do you like or dislike about online discussions?

3. How many of you actually go online to try to initiate or participate in a scientific discussion vs. just downloading papers, buying chemicals, or looking at the latest lolcat?

4. On a related note, what tips the balance for you from just taking in information to contributing it (and vice versa)?

5. For those of you who self-select as chemical biologists, would a chemical biology blog offer something unique as compared to other blogs, news sites or discussion groups you know of? Would you read/participate in a chemical biology blog?

Like Neil (and the chemistry team), we’d really love a ‘deluge of posts’ about this, whether you’re out on your own limb or not (yes, another reference to the platypus…). Thanks for your help!

Catherine (and the rest of the Nature Chemical Biology team)

Reactions – Penny Brothers

1. What made you want to be a chemist?

Science ran in my family – my father was a geology professor and my mother was a botanist. I used to visit my father at work and the geology department had display cases with beautiful crystalline minerals that used to fascinate me. The breakthrough came when I first encountered chemistry at school and found that I didn’t have to be limited to gazing at beautiful crystals in a glass case, I could make them myself!

2. If you weren’t a chemist and could do any other job, what would it be – and why?

I would be drawn to something that had a similar combination of being people-oriented, practically-oriented and involving lots of problem solving. After I was drawn into chemistry with its necessary hours of time spent in labs I became very interested in outdoor activities – not always a good mix. I have also always liked writing and reading and been interested in the publishing industry. How could I combine all of these? Maybe I should have been born 150 years ago and been one of those intrepid explorers that broke new scientific ground by travelling to exotic places and observing and documenting what they found there.

3. How can chemists best contribute to the world at large?

The solutions to the major problems facing the world at present – finding energy sources that can provide quality of life for the world’s population without further damage to the environment – will be chemical solutions. Particularly in the area of energy and sustainability it is chemists who are defining the problems and seeking the answers.

4. Which historical figure would you most like to have dinner with – and why?

Alfred Stock. I teach and research in boron chemistry and it amazes me how Stock managed to achieve such a wealth of chemistry, preparing and handling toxic and air-sensitive compounds without the benefit of our present-day sophisticated equipment and analytical tools.

5. When was the last time you did an experiment in the lab – and what was it?

It depends on what counts – yesterday I helped an undergraduate student in the teaching lab crystallise her nickel complex. The last time I did a real experiment in the lab would have been in 1993 on sabbatical leave with Phil Power at UC Davis.

6. If exiled on a desert island, what one book and one CD would you take with you?

The book would be the Bible – good ripping yarns, narrative history, lots of pages with fine print so it would be a lengthy read, and maybe have some handy advice for coping with the spiritual and psychological side of being exiled on a desert island. The CD would be Handel’s Messiah – similar reasons, music that goes from the depths of despair to the heights of joy, plus I could sing along to the alto part.

Penny Brothers is in the Department of Chemistry at the University of Auckland, New Zealand, and works on porphyrin and corrole complexes containing two boron atoms, which show unusual structural and reactivity at both boron and the ligands.

NChem Research Highlights: viscosity, nanotrees and solid-state synthesis

Morning everyone, here are this week’s research highlights:

Viscosity is a property that’s easy to think about on the bulk scale (pouring syrup compared to water, for example), but it’s less easy to get your head around it on a molecular scale. But using a molecular rotor, viscosity can be measured within cells…

Heard of the Eshelby twist? No, it’s not a 1950s dance craze, but a type of crystal defect, and it can be exploited to make some very pretty looking nanotrees

And finally this week, a subject quite dear to my heart: solid-state synthesis. Having spent rather a long and frustating time during my PhD trying (and failing) to make a whole raft of compounds that calculations predicted should exist, I’m glad to see that other people have been successful in making a new polymorph of lithium bromide — exactly as predicted.

Enjoy.

Neil

Neil Withers (Associate Editor, Nature Chemistry)

Chemiotics: Do you know where your drug is (and what it is doing)?

Posted on behalf of Retread

Reading the biomedical literature is like reading a large Russian novel with thousands of characters who interact in unexpected ways. A recent paper [Nature Medicine vol. 14 pp. 382 -391 (2008)] brings together 3 such actors — CFTR, the protein mutated in cystic fibrosis, ceramide, a molecule only of interest to neurologists until recently, and amitriptyline, a drug for depression whose mechanism of action was (seemingly) known.

Let’s start with CFTR, a huge protein (1480 amino acids). CFTR mutations cause cystic fibrosis, the commonest hereditary disease of Caucasians. There must be some selective advantage to CFTR mutations as over 600 were known as of 2003. However just one accounts for >50% of all cases. It is a deletion of phenylalanine at position #508 (showing just how delicate protein structure and function really is). One guess is that the mutants protect against intestinal pathogens (infantile diarrhea kills many children in the developing world).

Ceramide and its derivatives contain two saturated unbranched hydrocarbon chains (16–20 carbons long). They are found in myelin (the wrapping of nerve fibers) which is mostly lipid. All sorts of awful hereditary neurological diseases (usually affecting children, but fortunately rare) are caused by the accumulation of molecules containing ceramide. In recent years, ceramide’s effects on non-neuronal cell proliferation and/or cell death have become prominent. Ceramide is a second messenger. The intracellular effects of ceramide in the normal workings of the brain haven’t been much studied.

Amitriptyline (Elavil) was one of the earliest antidepressants. We all knew how it worked; by blocking the re-uptake of neurotransmitters such as serotonin and norepinephrine from the synapse (except that this is an acute effect and this class of drugs — the tricyclic antidepressants — takes a few weeks to work).

Surely you see how all this fits together at this point. No? I didn’t either. Read on…

It turns out that CFTR mutations increase the levels of ceramide inside the lungs (the primary site of infection in cystic fibrosis). This is caused by alkalinization of the intracellular sites where ceramide is broken down. Elevated ceramide levels are thought to increase cell death, resulting in lung infection (the bacteria have more to munch on).

Where does amitriptyline fit in? It lowers lung ceramide levels. How? By decreasing the amount and/or the activity of an enzyme (acid sphingomyelinase) which breaks down a precursor of ceramide. The paper is silent on the mechanism(s) by which this happens (but does give two references #24, #25). Treating transgenic mice with mutant CFTR with amitriptyline decreases the frequency and severity of their lung infections. Amazing.

Where does the effect of amitriptyline on neurotransmitter re-uptake fit into all of this? It doesn’t, and that’s just the point.

Nowadays, medicinal chemists design organic molecules to fit into slots of proteins whose function they are trying to alter. The tricyclic antidepressants weren’t discovered this way (they are much older), but papers like Mol. Pharmacol. vol. 50 pp. 957–965 (1996) found crucial amino acids in the re-uptake protein to which they bound. A fairly open and shut case for their mechanism of action.

Except it isn’t. Who knows how many designer drugs are really working the way we think they do. A cautionary tale indeed…