RACI National Congress Day 4

Welcome back to our ongoing coverage of the 2014 RACI National Congress. So far the week has been characterised by exemplary plenaries each morning and Day 4 was no exception. To top it off, the student attendees were once again treated with a panel discussion by some plenary speakers. I also want to give a shout-out to fellow blogger/tweeter Renée Webster who gave an excellent presentation on her fuel oxidation research.

Makoto Fujita, The University of Tokyo – “Crystalline sponge method : X-Ray structure analysis without crystallization”

Imagine this – you have an unknown compound (< 1 mg), NMR is inconclusive, so is the mass spec data. Fujita presents a future where as little as 5 nanograms could be used to unequivocally determine it’s structure. Forget painstakingly growing a crystal – just soak it into Fujita’s crystal-sponge and wait. It can take approximately 2-7 days for the networked structure to equilibrate and accomodate the guest in an ordered fashion. When I asked Fujita whether he had considered commercialisation of his “crystal-sponge”, this was the response:

“You know the Apple iPhone? They first released the iPhone 3. Our crystal is the iPhone zero.” – Makoto Fujita

So, clearly there is still a lot of work to be done in generalising this method. Derek Lowe commented this week that in his experience the network is completely incompatible with basic amines or heterocycles. Fujita says that occupancy within the crystal of 40-70% gives a “semi-empirical structural solution” and >70% gives data comparable with conventional X-ray. The response to Fujita’s paper in Nature last year has been huge and it appears a number of groups are working on validating/improving the technique. Perhaps one day the “crystal-sponge” will be something every lab couldn’t do without.

Success in Research Panel – David Leigh, Alan Aspuru-Guzik, Hubert Girault, Katharina Landfester

Most of the questions in the second plenary discussion panel on thursday appeared to be geared towards how to best put ourselves forward in a resume/CV. The academics outlined what they look for in a candidate – creativity, enthusiasm and leadership. The cover letter is crucial and should be genuinely personal (it cannot be a carbon-copy for all applications). Where possible, meeting an academic in person (eg. at a conferences) is ideal. A face to face meeting can go a long way in building a relationship.

Aspuru-Guzik said he looks for what he calls “triangulation”, a bachelor at one university, a PhD at a different one and a post-doc at yet another. Each preferably with different research focuses. Commenting on research record, it was suggested that you should avoid publishing multiple papers with similar titles. You should show breadth and creativity where possible. Don’t drip feed your research by publishing many small papers as apparently “1 JACS is worth 5 Chem Comm’s”. Ouch.

In the end, the picture is similar to yesterday. A good record, a good recommendation, a good cover letter, leadership skills and creative personality. In the words of David Leigh, “Don’t be afraid to be incredibly ambitious”.

RACI National Congress Day 2

Hi guys! Welcome back to day 2 of my RACI congress summary. Once again here is a simple outline of my top 3 talks of the day:

1. David Leigh, The University of Manchester – “Making the tiniest machines”

Out walks David Leigh with coloured cloth in hand, he paces back and forth across the stage. After a short introduction, he opens his hand and the cloth is gone. For those that don’t know, David Leigh is clearly quite the magician – both on stage and in the lab. Leigh described one of the first examples of a “molecular machine” to produce a peptide/protein molecule. Using a supramolecular catenane strategy, a series of amino acids were coupled together using chemical ligation. It will be very interesting to see how this can be applied to large proteins/peptides as opposed to more simplistic models.

2. James Crawford, Genentech – “Potent and selective pyridone BTK inhibitors with activity against mutant forms of BTK”

Building on the work of Roche, Crawford outlined the latest by Genentech for their work toward a BTK inhibitor. Some small molecule structures were described for the first time. A BTK inhibitor was developed using X-Ray crystallographic methods in combination with computational models and what Crawford describes as “Matched Pair Analysis”. This modern technique involves looking at a single property in a series of molecules in which a single functional group is changed/modified. Monitoring the trend of these properties across the series can then drive the med-chem direction of the project. Strikingly, kinase activity/selectivity was constantly monitored throughout the project.

3. Shane Wilkinson, Sydney University – “Synthetic Cannabinoids : from “drug design” to “designer drugs””

The huge explosion of designer drugs has lead to the rapid implementation of “hit to market” drugs – in direct contrast with the “hit to lead” theme in which Wilkinson found himself. An awesome talk on a vast series of street drugs currently being dispersed into the public domain via questionable characters in the illicit drug scene. Shane has synthesised a huge number of these compounds and tested their affinity for the “promiscuous” cannabinoid receptor. The most striking message of the talk was the ability of illicit manufacturers to use academic and patent literature as inspiration for their own organic syntheses. Shane even outlined a few cases where molecules seen were clearly a combination of two “chunks” of literature molecules. In other words, a “molecular hybridisation” of literature compounds.

Tune in next time for a “Baran” spectacular and/or outline from the excellent panel discussion on success in academic careers.