Last night I went to a public lecture at the University of Surrey organised by the Royal Society of Chemistry. Professor Ian Wilson spoke on the topic: “Mapping the Phenome: The analytical chemistry of life”.

I receive email alerts of talks like this, and was alerted by the fact that this was a topic that I was interested in (I have a past as a natural products chemist, and I edit quite a lot of metabolomics protocols), and that it was going to be happening in Guildford (which is closer to where I live than London is!).

The first comment to make is that this was a public lecture, so it was pitched at the level of an intelligent, interested person who had not necessarily had any formal scientific training. This talk was definitely a success; whenever I looked at the other people around me they were attentive and smiling.

The title of the talk mentions the phenome which, I suppose, looks at different phenotypes (as apposed to genotypes). As we know, organisms are somehow a product of their genome and their environment, and the point where I laughed and laughed was when he referred to the compounds that the organism is exposed to as being the “exposome”.

One part of the phenotype of an organism is its metabolome, and that was the main focus of the talk.  The title could equally easily have been: “Metabolomic analysis of urine” or perhaps “Pisse prophets of the past, present and future”.

Woodcut showing a wheel and chart that classify urine samples, shown in the blog: “Medium Aevum”.

Professor Wilson had a wooden rack for screw-top test-tubes which he opened and sniffed during the first part of his talk. He concluded this act by drinking one of them! While they all looked they might possibly be urine, they were in fact: coffee, pepsi, two strengths of tea, and scotch. He drank the scotch, apparently.

For the rest of the talk, he showed a lot of NMR spectra from urine samples of mice, rats and humans:

600 MHz 1H NMR spectrum of control rat urine, displaying hundreds of resolved peaks

… and Principle Component Analysis plots:

I know, I know, it is actually from a protocol for NMR of plants, but it is the nicest image that I can find in our content that looks like what Prof. Wilson showed in the talk.

At no point did he get bogged down with how the samples were prepared, what NMR was, or even what principle component analysis involved. What he emphasised was pattern recognition, and how you could start to see patterns in the NMR spectra for different mouse types, treatment groups, or people with different diets.

There was a feeling of optimism that this type of analysis would ultimately result in clinicians being better able to choose for each patient the best drug out of an array of possible treatments (i.e. the one most likely to help, and least likely to cause harmful side effects), because clinicians would be able to determine which pattern-group the patient belonged to.

With the advent of technologies that have made large-scale genome sequencing projects possible and since a stream of high-throughput biological assays have been developed to collect, for instance, data on proteomics, metabolomics and gene expression, the need for ever more advanced, powerful and sophisticated bioinformatics tools has become an increasingly stringent fixture of today’s molecular biology research.

The Mathematical and Statistical Aspects in Molecular Biology (MASAMB) meeting has brought together every year since 1989 a relatively small number of researchers (usually around 100) from the fields of mathematics, statistics, computer science, bioinformatics, and biology to discuss and exchange ideas on methodological and applied research in an “intimate” workshop setting. This year’s MASAMB will take place on April 11^th and 12^th at Imperial College London, with the main topics of discussion being statistical bioinformatics, computational cell biology, next-generation sequencing, systems biology, and evolution.

Since their birth in 2006, both Nature Protocols and the Protocol Exchange (which was originally called the Protocols Network) have published a steady flow of protocols that can be categorized under the general term “computational biology”. Unsurprisingly, some of these protocols have proven very popular with our readership, with a number of these articles ranking among the journals’ most cited papers.

As we anticipate the number of published protocols in this field to increase further — as well as the interest in them from our readers — for the first time this year, we have decided to attend as a journal MASAMB, sending along one of our associate editors, well, sending along myself, Baldo Lucchese. I will be covering the workshop for Nature Protocols attending as many talks as possible and speaking to as many researchers and, hopefully, readers as humanly feasible. The objective will of course be to gain the wherewithal to make Nature Protocols a more helpful source for researchers in bioinformatics and statistical genetics and for readers with an interest in these fields. It will also be an excellent opportunity for me to meet in person a few of our authors. I certainly look forward to that too.

If you too are going to be at the conference, please do come by to say hi.

Stay tuned for the next blog post on this issue after I come back from MASAMB XXIII.

At the end of March, Dot and I spent two days in Edinburgh at the Select Biosciences meetings held at the Edinburgh Conference Centre on the Herriot-Watt campus, about 6 miles outside the city centre. The weather was record-breakingly hot for March (and Scotland!) – here is some evidence of the spring sunshine:

We didn’t have too much time to enjoy the weather though as there were four concurrent meetings to attend; I spent almost all of my time at the Single Cell Analysis Europe conference, while you will receive further reports from Dot on talks from the Lab-on-a-chip European Congress, Advances in Microarray Technology, and Advances in Biodetection & Biosensors sessions.

As an editor, I found the meeting really interesting, with some of the top names in the field speaking and methodological advances a-plenty for us to learn about!  The exhibition hall was also a really interesting addition to the main sessions as we got to see a lot of the lab-on-a-chip and microfluidic equipment that people use in their protocols in real life for the first time! And they really are quite amazing!

Day one’s session on using microarrays and chips in single cell analysis started with a keynote presentation from Professor Marcus Textor from ETH Zurich, on the use of microfabricated cell culture platforms to study cell function and drug response in engineered 2D and 3D microenvironments. Describing how cell culture has moved on from the invention of the Petri dish in 1877, Professor Textor firstly showed how PDMS microwells can be engineered to provide 3D culture environments with varying substrate stiffness and shape, which can regulate the assembly of the actin cytoskeleton, impacting cell survival, phenotype and function. He also described the use of a PEG-based microwell platform to create 3D breast cancer models to allow responses to taxol and other anticancer drugs to be tested in vitro.

Dr. John Collins (NanoInk Inc.) then presented a talk on dip pen nanolithography as a technique for fabricating cellular microenvironments that allows single cell co-culture, and targeted delivery of agents such as drugs. As a work in progress, Dr. Collins also explained how they are using this technology to print substrates in lines rather than dots to enable the study of cell motility in this 3D microenvironment.

The next session, on label-free routes to single cell analysis started with an interesting talk from Professor Susann Müller (Helmholtz Centre of Environmental Research), which focused on assessing microbial community dynamics using flow cytometry and phylogenetics, encompassing analysis of even unculturable bacterial strains. Changes in the community cytometric fingerprint or structure over time can be measured and used as a biosensor for the state of natural environments, such as monitoring the stability of the enhanced biological phosphorous removal (EBPR) process in wastewater treatment plants as illustrated in this talk.

The afternoon began with the second keynote presentation, from Professor Nicholas Navin of the MD Anderson Cancer Center, which detailed the investigation of genome evolution in breast cancer by single cell sequencing. Combining flow-cytometric sorting, whole genome amplification and next-generation sequencing, this single nucleus sequencing (SNS) method can be used to accurately quantify copy number in single nuclei. Professor Navin’s group used SNS to analyse 100 single cells from a polygenomic tumour and 100 single cells from a monogenomic primary tumor and its liver metastasis, data from which indicates that tumors grow and evolve by punctuated clonal expansions, rather than gradual tumor progression. Look out for the upcoming Nature protocol on this method as we have this in production as we speak!

New and improved methods for DNA sequencing are clearly an up-and-coming area of methodological research and before moving on to the use of microfluidics in single cell analysis, the afternoon’s session continued with a talk from Professor David Bensimon (Ecole Normale Supérieure) describing a novel, single molecule method for the mechanical sequencing of DNA. This method uses a magnetic trap to mechanically open out and close DNA hairpins. In the presence of hybridizing complementary oligonucleotides, rehybridization of DNA hairpins is blocked, and the position of these roadblocks on single molecules can be measured with nanometer precision, allowing sequencing of the DNA molecule by hybridization or ligation: 

For further details on this new method, see the paper just published in this issue of Nature Methods (9(4), p367-372) [Update: this paper is now free to access for a week] and the News & Views piece by Sten Linnarsson in the same issue, from which the above illustration is taken. Another method for sequencing was also presented at the same time in the lab-on-a-chip meeting, using nanopore sensors for next generation DNA sequencing. Sadly my conference-going skills do not extend to splitting myself in half to be at two talks at once, so I was unable to hear about this new method in person as well!

Day two started with two talks on the use of RT-qPCR in single cell analysis, from Professor Mikael Kubista (TATAA Biocenter) and Dr. Ken Livak (Fluidigm). These highlighted the variation in gene expression levels found from cell-to-cell, even in seemingly homogeneous populations, caused by the stochastic nature of transcription that occurs in the cell in bursts. Both speakers presented methods that can be used to deal with this heterogeneity, the latter explaining why single cell data needs to be treated differently from conventional qPCR data, and how this can be achieved using multivariate analysis and considering factors such as replicates, limits of detection, normalization and data display.

A couple more very interesting methodological talks followed in the afternoon session on single cell analysis in signalling, from Professor Ola Soderberg (Uppsala University) and Frederik Fritzsch (Dortmund University). Professsor Soderberg described the application of the in situ proximity ligation assay (PLA) and padlock probes to visualize signal pathway activity in single cells. In situ PLA utilizes pairs of antibodies, with bound DNA sequences, to target interacting proteins. Proximal binding of the antibodies and the conjugated oligonucleotide sequences creates a circular DNA molecule that can be amplified by rolling circle amplification (RCA) and subsequently detected by hybridization of fluorophore-labelled probes. Padlock probes also use RCA to generate signals for detection and the two can be combined to allow multiplexed analyses. The Envirostat 2.0 was then presented by Frederik Fritzsch with plenty of impressive videos to demonstrate this new, negative dielectrophoresis-based system for contactless single cell isolation, cultivation and analysis.

All in all, the full program provided many stimulating talks in areas undergoing, and with great potential for, methods development. Although we cover protocols in these areas already, we are now full of new ideas for enhancing our content on these topics going forward, so watch this space!

Next week, Dot and I will be heading to Edinburgh to attend the Select Biosciences Single Cell Analysis Europe conference.  These days, the analysis of single cells is being increasingly applied to get to the bottom of experimental questions in biology, and is a rapidly expanding discipline, rich in methodological advances.  We are really looking forward to hearing about the techniques currently being used, as well as discovering new methods that are now being developed.

The conference will run over two days, 28^th-29^th March, and covers the use of microarrays, microfluidics and label-free approaches to study single cells, as well as the use of RT-qPCR in single cell analysis, among other topics.  Keynote lectures will be given by Norman Dovichi and Marcus Textor, and two of our very own Nature Protocols authors, Jay Groves and Nicholas Navin.  Although our single nucleus sequencing protocol from the latter is only just in production at the moment, we have a Nature protocol from the Groves lab. that describes the use of supported membranes and single-cell microscopy to investigate cell signalling. We also have a Nature protocol on RT-PCR data analysis from Kenneth Livak, which is relevant to his upcoming talk at this conference, and a Nature protocol from Susann Müller who will be speaking there too, describing how to use microbial community dynamics as a biosensor.

In advance of our attendance, we have put together a collection of our single-cell protocols for your interest, which will be free to access for the rest of this month, alongside those from our authors who will be speaking.  While this is only an example of our content on this topic, you will see that the protocols cover a range of areas from gene expression and copy number profiling to isolation and imaging of single cells and we hope that you will find them useful!

In addition, conference registration also allows entrance to three other concurrent meetings; the Lab-on-a-chip European Congress, Advances in Microarray Technology, and Advances in Biodetection & Biosensors.  Nature Protocols authors are again represented amongst the speakers at these meetings, with Mark Bradley (protocol in production), Andreu Llobera and Bo Mattiasson all giving talks.  As you can see, these meetings are also highly relevant to our scope and content at Nature Protocols so we are keen to make it to some of these sesions too.  There are only two of us, but we will aim to get to as many of the talks as we can and will bring you some reports shortly after our return!

Those of us who did a few months of mass spectrometry lectures somewhere in an undergraduate course sometime in the last century, and have had our eyes elsewhere since then, might find that this field is completely unrecognisable. Perhaps, like me, you did some GC-MS of organic compounds extracted from some matrix or used MS as one of the analytical tools to characterise a compound you synthesised. The extension of these ideas to metabolomics-type experiments, and even proteomics is not conceptually challenging (though I admit that the finer points are rather complicated), but the idea that you could use mass spectrometry to get information about the secondary or tertiary structure of a protein or a protein complex might seem far-fetched.

Let me state it boldly: Mass Spectrometry technology has moved on sufficiently that it can be used to look at the secondary and tertiary structures of intact proteins and protein complexes. It happened while I wasn’t looking. It happened a while ago.

An important theme from the  Mass Spectrometry Technologies for Structural Biology conference was the statement of where mass spectrometry fits into structural biology:

– X-ray crystallography provides a very high resolution image, but it is a static snapshot of one possible conformtion

– in NMR the structure seen is an average of the populations present

– the strengths of MS are that it can handle a high level of heterogeneity (and you can tease out many of the different structures) and that you can get dynamic information (on interactions and reactions)

MS spectrum of the yeast eIF3 isolated by tagging subunit eIF3b. Charge state series are assigned on the basis of masses to subcomplexes eIF3i:g, eIF3b:g:i, and eIF3a:b. eIF3i is observed dissociating from the yeast complex at ≈m/z 3,000. (Inset) The interaction network for yeast eIF3 derived from seven subcomplexes observed by MS. Taken from PNAS, 2008.

While Mass Spectrometry is in the title of this conference, and is the common theme throughout all of the experimental work, an important observation from the talks and posters is that the researchers do not use it in isolation. X-ray crystallography, for example, may provide information useful in interpreting the mass spectrometry data or electron microscopy might, for example, provide some information confirming the intermediates suggested by the mass spec results. For the most part, it seems that this is a community that forms strong collaborations.

The speakers were careful to define the instrumental set-up and the potential limitations of their experiments, and there were very lively discussions on these points during the question-times. It is a community that cares deeply about the rigour of their methods.

While I enjoyed the talks, a lot of the detail went over my head. I would therefore very much like to thank some of the PhD students and post-docs who very kindly walked me through their posters, and patiently answered my questions.

At Tampa airport, after a 10-hour flight:

Custom Official: So. Is the trip business or pleasure?

Me: Well. It’s somewhere between business and pleasure. I am going to a conference at St Pete’s Beach.

Custom Official: <PAUSE><NO SMILE> Always just tick the “Business” box on the landing card, because there is a limit on the number of allowed vacation days.

I very much enjoy conferences: listening to talks, asking people to “walk me through” their posters and generally allowing myself to be carried along by the enthusiasm that scientists have for their work. The recent Mass Spectrometry Technologies for Structural Biology was no exception; and the location at this time of the year meant that every amount of spare time could be spent in the sun without it being too hot.

The trolley service was good, though rather informal in comparison to London buses, and I was able to get to the main St Petersburg town and Pass-a-grille (in the opposite direction) quite easily. If you find yourself at St Pete’s Beach and have limited time (say two hours round sunset), I would definitely recommend Pass-a-grille as it is a lot closer, it is very pretty, and you will be able to find a restaurant right next to the beach without breaking a sweat.

I am very excited about going to Florida for the Mass Spectrometry Technologies for Structural Biology Conference organised by the American Society for Mass Spectrometry. To celebrate, five of our related protocols will be free for a few weeks.

Ion mobility–mass spectrometry analysis of large protein complexes
Brandon T Ruotolo, Justin L P Benesch, Alan M Sandercock, Suk-Joon Hyung & Carol V Robinson

Determining the stoichiometry and interactions of macromolecular assemblies from mass spectrometry
Helena Hernández & Carol V Robinson

Multiplex peptide stable isotope dimethyl labeling for quantitative proteomics
Paul J Boersema, Reinout Raijmakers, Simone Lemeer, Shabaz Mohammed & Albert J R Heck

Chemical derivatization of histones for facilitated analysis by mass spectrometry
Benjamin A Garcia, Sahana Mollah, Beatrix M Ueberheide, Scott A Busby, Tara L Muratore, Jeffrey Shabanowitz & Donald F Hunt

A sensitive mass spectrometric method for hypothesis-driven detection of peptide post-translational modifications: multiple reaction monitoring-initiated detection and sequencing (MIDAS)
Richard D Unwin, John R Griffiths & Anthony D Whetton

So I have finally finished collecting my thoughts from the 3rd EMBO meeting in Vienna, which I was fortunate enough to attend from the 10th-13th Sept.

Hosted in the Austria Centre Vienna

the meeting was attended by around 1300 people, and with over 600 posters and 21 concurrent sessions there was lots to keep participants busy! As my first conference experience for a good few years, it was a little overwhelming, but in a good way!

Vienna

I found Vienna to be a lovely city, as was the weather for the weekend, which helps with the laid back atmosphere…

The architecture is amazing, with beautiful buildings on every corner

and although it was a little too cultural for my time-frame with many art galleries and museums that I didn’t manage to see, I did appreciate my visit to see the living art of the Spanish Riding School! Sadly we weren’t allowed to take pictures of the action, but here is one of the stars dozing in the sun

Anyway, on to the conference, which began with a series of plenary lectures on hosts & microbes, including a really interesting talk by Bonnie Bassler who explained their work investigating quorum sensing inhibitors as potential therapeutics to prevent pathogenesis. Although there is still some way to go before inhibitor compounds are made into drugs, this sounds like an exciting avenue of future research, especially given the multidrug resistance problems nowadays. I also really enjoyed the final talk in this session from Brett Finlay (despite the high content of toilet humour!) on the importance of our gut microbiota in our health and their role in resistance to allergic diseases such as asthma.

For the next 3 days, there was a great diversity of topics presented so I was too often spoilt for choice about which session to attend! Day two started with an excellent keynote lecture from Susan Lindquist discussing the role of protein folding in the inheritance of environmentally acquired traits via both Hsp90- and prion-mediated mechanisms. She explained how Hsp90 buffers the effects of genetic variation and acts as a potentiator of evolution, enabling previously hidden genetic variation to be revealed in times of stress. In the plenary session on genome evolution that followed, Paul Rainey presented evidence of the involvement of an epigenetic switch in bacterial genome evolution, reinforcing the theme that genome evolution is about so much more than just the underlying genetic variation.

Next-generation sequencing

Another theme that spanned many sessions was the use of next-generation sequencing and the advances made possible in a variety of fields as a result of the development of these techniques. This was illustrated by Mike Stratton’s plenary lecture on the exome sequencing and analysis of cancer genomes. Hand-in-hand with such technological advances of course comes the need for methods to analyse the vast quantities of data produced. These ideas were further explored in the session on human genome variation & disease with a talk from Elaine Mardis covering whole genome sequencing approaches used to analyse cancer genomes, including their application to personal diagnosis and treatment.

Personal medicine

Continuing on the topic of personal medicine, Russ Altman from Stanford next introduced a pharmacogenomics database designed to allow the effect of human genetic variation on drug responses to be assessed. This became quite entertaining when he reported results from the analysis of the personal genome of his colleague, Steve Quake; he had obviously agreed to everyone at EMBO and beyond knowing how he is likely to respond to a variety of drugs as well as his genetic predisposition to various diseases, but it is quite wierd to feel like I know far more about his genome than about the man himself?!

Computer vision

As well as the increase in the throughput of sequencing methods, there is also now a need for computational methods to keep up with advances in imaging methods. This was explored in a stimulating session on computer vision of cellular function in which Andre Brown and Sean Megason (amongst others) described systems to image C. elegans behaviour and zebrafish embryo development, respectively, as well as outlining the software they designed to analyse the image data obtained. The real take home message from this session was that it’s no use having the means to obtain data on this scale if you don’t also have algorithms and software to enable efficient and accurate analysis of this data to extract the biological meaning. So I think this will be a big area for methods development going forwards.

TNTs

I also found a new area of molecular biology to me and was really interested to learn about the recent discovery of tunneling nanotubes (or TNTs). In a talk by Hans-Hermann Gerdes we heard how these nanotubes form and that they are used for long distance electrical coupling between cells, and as a method of cell-cell communication for the transfer of cytoplasmic molecules and organelles. Fascinating stuff!

And finally, the prize for the best talk goes to…

Florian Engert, for his virtual reality world for zebrafish larvae. Or as he put it, ‘The Matrix’ for fish! He presented work on adaptive motorlearning in zebrafish larvae and detailed the system he developed in which larvae are paralyzed and surrounded by a virtual reality environment, which allows the whole brain to be imaged at a single cell level in an awake animal as they respond to experimentally induced changes in the environment. This clearly provides an exciting system to study the neural circuitry underlying a range of visually-induced behaviours in zebrafish.

Featured protocols

I will finish with a reminder of a couple of Nature Protocols that I was really pleased to spot being put to good use in the work presented at EMBO.

Firstly, “CO-FISH “:https://www.nature.com/nprot/journal/v5/n7/full/nprot.2010.102.html (chromosome orientation fluorescent in situ hybridization) was being utilised by both Shahragim Tajbakhsh and Peter Lansdorp in their talks on the non-random segregation of chromosomes in mitosis.

And genomic SELEX formed the basis of the work presented in Renee Schroeder’s talk in the RNA & RNA mediated regulation session.

Having left my meticulously drawn maps and notes on the dining room table, I boldly set off to Cambridge for the Synthesis in Organic Chemistry Symposium. I was immediately confronted by three Universal Laws:

1. If a bed-and-breakfast is within a 100 m radius of a person’s home, said person is unlikely to know of its existence.

2. People driving swish cars seldom know the directions to the nearest train station (or anything else regarding public transport).

3. Turning right instead of left can have consequences significantly exceeding the ease with which the mistake can be made.

Despite these obstacles, I found Vine Farm, and later the train station, the important bus stops, and Churchill College itself.

After a moderately sunny weekend, the days of the conference were cold, overcast and windy: perfect weather to take shelter in a lecture theatre and escape into the wonderful world of organic synthesis. I was pleasantly surprised to find that I understood enough of the chemistry to follow most of the talks and found myself wishing that I could be in the lab again.

Themes that emerged, at least in my own mind, were:

1. Flow Chemistry and Automated Synthesis.

Steven Ley has developed many flow chemistry methods, and talked about using these systems for reactions where the method has already been optimised and where a compound needs to be prepared in bulk, to allow the valuable minds and skills of PhD students and post-docs to concentrate on new reactions. Vapourtec had a stand to demonstrate their instruments plus an impressive list of publications where their machines had been used many of which had Steve Ley’s name in the author list.

The ReactIR Flow Cell was also mentioned in Helma Wennemers talk in the context of looking at reaction mechanisms.

Peter Seeberger also talked about automated synthesis, this time for the synthesis of oligosaccharides in an approach analogous to that of automated peptide synthesis. His protocol Continuous-flow reactor-based synthesis of carbohydrate and dihydrolipoic acid-capped quantum dots is being published on our site this week.

2. Emergence of kits to perform catalytic reactions.

Prof. Buchwald spoke about the palladium-catalyzed cross coupling reactions that his group has developed and studied, revealed how the ligand names were derived (named after labmembers (e.g. BrettPhos after Brett Fors) and his cats (e.g. RuPhos after Rufus)) and that he was working with Aldrich and STREM to provide the catalyst reagents in kit form.

Both STREM and another company, Johnson Matthey Catalysts had stands at the conference. Johnson Matthey Catalysts provide kits for performing a range of reactions, including those catalysed by enzymes.

3. The pervasive use of SciFinder.

SciFinder was in fact mentioned in the very first talk by Larry Overman, and quite often in conversation during the course of the conference. It is affiliated with the American Chemical Society and I gather that it was a database containing metadata for chemistry-related articles – similar in a way to PubMed, but with more functionality (including the ability to search by chemical structure) and a price-tag. I was relieved to find that Nature Protocols was present in the database!

4. The Holy Grail of 100 % ee

Unsurprisingly, almost all of the compounds-of-interest were chiral, and their successful synthesis required developing enantioselective reactions. Helma Wennemers, for example, talked about her work on developing catalysts that are based on the chemistry of the active sites of enzymes.

And Finally

While all of the talks were excellent, the one that was most memorable was Eiichi Nakamura’s “Imaging of Single Organic Molecules in Motion”. I am not sure how I managed to miss the publication of the original papers, but watching the electron microscopy videos of molecules wiggling through or on top of nanotubes was very pleasing indeed (see also this JACS image challenge).

Alkenyl fullerene in a carbon nanotube

And the most entertaining talk – which included various magic tricks! – was that given by David Leigh on “Making the tiniest machines”. The machines he described were based on catenanes and rotaxanes, which are both examples of interlocked molecules. Again, I am not sure what rock I was trapped under not to notice the original publications, but these images might whet your appetitie if you also somehow managed to miss them.

from A synthetic small molecule that can walk down a track_

from A molecular information ratchet_

Today, I am in a good mood, because I know that next week I am going to a conference! As much as I love looking at manuscripts and browsing through the literature for commissioning ideas, it will be good to be out of the office and listening to scientists talking about their work. Hopefully, I will get to meet and chat to a few as well! I will be staying in a little bed-and-breakfast in the evenings, and during the day I will attend talks by eminent chemists at the 22nd International Symposium: Synthesis in Organic Chemistry in Cambridge.

Is anyone else going to the meeting? If so leave a comment and I’ll make sure to look out for you. Or just come and say hello when you are there.

To highlight our chemistry content, the following protocols have been made open access until the end of July.

Protocols relating to metathesis:

Synthesis of N-heterocyclic carbene ligands and derived ruthenium olefin metathesis catalysts

Xavier Bantreil & Steven P Nolan

Synthesis of all-hydrocarbon stapled α-helical peptides by ring-closing olefin metathesis

Young-Woo Kim, Tom N Grossmann & Gregory L Verdine

Solid-phase synthesis of short α-helices stabilized by the hydrogen bond surrogate approach

Anupam Patgiri, Monica Z Menzenski, Andrew B Mahon & Paramjit S Arora

Olefin cross-metathesis-based approaches to furans: procedures for the preparation of di- and trisubstituted variants

Timothy J Donohoe, John F Bower & José A Basutto

Click chemistry

Alkyne-azide click reaction catalyzed by metallic copper under ultrasound

Pedro Cintas, Alessandro Barge, Silvia Tagliapietra, Luisa Boffa & Giancarlo Cravotto

More Click Chemistry protocols can be found here

Enzyme catalysed

Preparative scale Baeyer-Villiger biooxidation at high concentration using recombinant Escherichia coli and in situ substrate feeding and product removal process

Iris Hilker, Maria C Gutiérrez, Roland Furstoss, John Ward, Roland Wohlgemuth & Véronique Alphand

Other useful reactions

Pd-catalyzed Suzuki-Miyaura reactions of aryl halides using bulky biarylmonophosphine ligands

Ryan A Altman & Stephen L Buchwald

The partial reduction of electron-deficient pyrroles: procedures describing both Birch (Li/NH3) and ammonia-free (Li/DBB) conditions

Timothy J Donohoe & Rhian E Thomas

The use of the Ugi four-component condensation

Stefano Marcaccini & Tomás Torroba

Synthesis of specific reagents

A practical guide to the synthesis of dinitroindolinyl-caged neurotransmitters

Graham C R Ellis-Davies

A concise and scalable route to L-azidohomoalanine

Stefanie Roth, William C Drewe & Neil R Thomas

Analytical techniques

A method for concurrent diazomethane synthesis and substrate methylation in a 96-sample format

Lana S Barkawi & Jerry D Cohen

Methods for isolation, purification and structural elucidation of bioactive secondary metabolites from marine invertebrates

Sherif S Ebada, Ru Angelie Edrada, Wenhan Lin & Peter Proksch

Mosher ester analysis for the determination of absolute configuration of stereogenic (chiral) carbinol carbons Thomas R Hoye, Christopher S Jeffrey & Feng Shao