The “National Fresenius Award Symposium” celebrates researchers that have made amazing early career advances; this year the award went to Neal K. Devaraj, and this session was assembled in his honour.

The session started with a talk by David Chenowerth on making synthetic collagen. Collagen is a peptide triple helix made of peptide chains of the general form: [Gxx]3. His group has been doing experiments replacing carbon atoms with nitrogen – e.g. using aza-glycine instead of glycine in one (or more) of the repeating triplets Proline-Hydroxyproline-Glycine – which has remarkable effects on the stability of the resulting triple helices.

After a fascinating talk from Dale Poulter about exploiting the versatility of farnesyl transferase for the preparation of protein microarrays, there were three talks about lipid bilayers.

Steven Boxer spoke about recent work on tethered lipid bilayers – using a really clever approach using lipid-DNA conjugates with complementary DNA strands – which has been applied to looking at membrane fusion of enveloped viruses.

For imaging organelles, you could label either the membrane proteins or the lipids. An advantage of labelling the lipids is that there are many more lipid molecules than proteins in the membrane, so if you choose a photostable fluorophore that blinks spontaneously it should be possible to image for longer time periods before you get photobleaching. Alanna Schepartz spoke about work using an environmentally sensitive (fluorescesces more at low pH) fluorophore (Sir-Tz) to image things like Golgi and ER using STED.  The Supplementary Movies are remarkable both for the resolution, and for the length of time of the imaging experiment.

The last talk was by Neal Devaraj who spoke about his work on in situ synthesis membrane synthesis. So what does this mean? He creates clickable phospholipid precursors, sets up the reaction and watches how new lipid vesicles form over time. To solve the problem of catalyst dilution over time, they developed a really neat system for continual synthesis of a catalytic membrane.

Image taken from: 10.1073/pnas.1506704112, Hardy et al. (2015) PNAS 112  pp 8187-8192

They have also done some exciting work towards synthetic re-modelling of lipid bilayers using a reversible covalent coupling. Remarkably it is possible to see the formation of microdomains!

Image taken from: doi: 10.1073/pnas.1605541113, Brea et al. (2016) PNAS 113 pp 8589-8594

Dear Mother,
I have some exciting news! I am in San Francisco attending the American Chemical Society Spring Meeting.

I made the rather unusual decision to stay at a youth hostel this time: the Pacific Tradewinds. As it turns out, there are quite a few attendees staying here – in fact 4 of my 5 room-mates are going to be walking with me this morning to the Moscone Center!

There are many parallel sessions, and we all have the impossible task of choosing between excellent options. The program runs to 607 densely printed pages; so getting the conference app was a big help.

Yesterday I discovered that there is this booth – called Café-X – in a building near the Moscone, where you can have coffee made and delivered to you by robot; so you can guess what I will be doing every day this week!

Yours etc.
Bronwen

At the start of last month I headed to Singapore for the ISSCR Regional Forum “Global Controls in Stem Cells”. I had a great time and found the meeting a big improvement on last year’s Florence meeting, due to the increase in networking opportunities.

There was a lot of epigenetics at the meeting – as you’d expect given the topic focus. Several people showed the classic Waddington depiction of the epigenetic landscape and explained the need to define where in the landscape the various cell types present during human development lie, plus the different varieties of artificially engineered stem cells. It was fascinating to hear about the various different approaches being taken to address this question.

I don’t have the space to discuss every talk, so here is a brief summary of the sessions and some of the talks.

The first keynote of the meeting was from Rudolf Jaenisch. He started by talking about naïve versus primed embryonic stem cells (ESCs) and whether there is a single human naïve state. He then moved on to talk about finding disease-relevant phenotypes, for example using patient-derived induced pluripotent stem cells (iPSCs). He particularly focused on the need for an appropriate control, he favours an isogenic control to control for genetic background.

The first session was focused on reprogramming, with various researchers talking about their attempts to improve reprogramming and to dissect reprogramming pathways. Jonathan Loh talked about the miniaturised reprogramming system using 384 well plates his group has developed to aid this process. Hongkui Deng finished the morning talks with a fantastic talk about reprogramming human fibroblasts to hepatocytes with drug metabolic function. Up until now reprogrammed hepatocytes have lacked this function, which is so important if hepatocytes derived in this way are going to be used for drug screening.

After lunch there was a session on chromatin dynamics. Bing Ren focused on the functional analysis of transcriptional enhancers and developing a new way to look at gene regulation from a 3D point of view. Sung Hee Baek talked about chromatin modifiers in epigenetic control of cancer and stem cells. Ken Zaret talked about the initiation of cell reprogramming, specifically his efforts to identify “Pioneer factors”, these bind to target genes that will turn on later. The final talk in this session was from Ralf Huss, about using stem cells as drug delivery tools in cancer therapy, due to their propensity to home in on the tumour.

The first session of day 2 was devoted to the developmental biology of pluripotency. Ron McKay, one of the conference organisers, spoke on the need to understand the functional identity of human genomes. Many early lineage cell types can be grown, and the human ESC are all quite different. This variation needs to be understood. Sara-Jane Dunn talked about her computational work modelling pluripotency, an alternative approach to investigating this biological phenomena.

The first session after lunch was on Telomere and RNA biology. V. Narry Kim spoke first. The main focus of her lab is miRNA regulation, but in this talk she talked about RNA-binding proteins in ESC. Next up was Didier Trono who talked about how transposable elements and their epigenetic control mechanisms are key regulators of transcriptional networks in PSCs. Yue Wan talked about the importance of RNA structure in determining RNA function, and the need to learn more about RNA structure. Toshio Suda talked about the aging of hematopoietic stem cells. Stem cells are long lived, and they do change as they age. He talked about the different characteristics of “elderly” stem cells.

The first session of Friday morning was focused to Functional Genomics. Huck Hui Ng gave the first talk, on his work investigating the systems biology of stem cells. Andras Nagy talked about his groups attempts to produce a stable pluripotent cell quite different from ESCs. Frank Buchholz talked about using RNA screens to find modulators and regulators of the pluripotent state.

After lunch there was a Cancer session, covering a wide variety of aspects. Richard Young started the session with a talk about the roles of transcriptional super-enhancers in cell identity and cancer. Zsuzsanna Izavak talked about her recent Nature paper on transcription driven by primate-specific endogenous retrovirus HERVH in naïve stem cells. The HERV driven network partially explains differences in mouse and human stem cells. The significant differences between mouse and human stem cells were mentioned by several of the speakers throughout the conference. Jesse Smith talked about gene transcription inhibitors as potential cancer therapeutics. The rationale being that cancer can be viewed as a disease of de-differentiation, i.e. dysregulated gene transcription.

Yukiko Gotoh talked about regulation of neural stem / progenitor cell fate in the embryonic and adult mouse brain. The basic premise of her work is that embryonic neural stem cells build a brain, whilst adult neural stem cells have a very different role, e.g. in learning and memory.

Janet Rossant gave the closing keynote lecture. She talked about cells in early embryo development and studies looking at when developmental potential is lost, comparing the mouse and human embryo. She also emphasised the differences between mouse and human early embryo development, and the importance of remembering this when studying stem cells.

I very much enjoyed my time in Singapore – it really is a beautiful city. I attended the night safari on the conference networking trip, which was great fun and a really unique experience. I even managed to secure a gift for my children left at home – a lego “Mr Stem Cell” so I can introduce them to the delights of stem cells at an early age!

In the shadow of The Shard at the end of August, I joined about ~120 scientists at KCL for the 4^th Single Molecule Localisation Microscopy Symposium. This 3-day meeting preceded the announcement in October that the Nobel Prize in Chemistry had been awarded to Eric Betzig, Stefan Hell and William E. Moerner for their contributions to the field of super-resolution (SR) microscopy (which includes SMLM approaches), but it was already very clear from the content and calibre of the programme that the field was having an important impact on several key areas of biological research.

The Symposium was superbly organized by Helge Ewers, Mike Heilemann, Aleksandra Radenovic, and Jean-Baptiste Sibarita; the only real disappointment being the cancellation of Stefan Hell’s keynote lecture due to illness. The 25 talks were divided into 5 broad topics: technical developments; biological systems; quantitative localization microscopy; labelling; and data analysis. It was particularly pleasing from my perspective that women researchers were well-represented, with at least 1 female speaker in all but 1 of the high quality sessions. Nature Protocols authors were also among the speakers^{1, 2}. The full schedule of talks can be found here.

I found most of the talks to be surprisingly accessible and, as someone very interested in techniques and methods, there was a lot to hold my attention. Much effort is being expended on improving SMLM with respect to: the achievable resolution, especially axially; its live imaging capabilities; and quantitative applications. Progress in all these areas largely relies on a combination of new microscope setups, improved labels, and advanced data analysis methods. Biological applications discussed included nanoscale clustering of membrane proteins (particularly during synaptic and T cell signalling in mammalian cells), molecular assembly/organisation of protein complexes, and single particle tracking. The talks were complemented by ~60 posters, which covered additional applications such as imaging the cytoskeleton, chromatin structure, and plant tissues.

But it wasn’t all hard work – attendees were treated to an evening boat trip along the Thames, which provided the opportunity for less formal discussions over dinner, whilst enjoying the beautiful views on offer. I spent a very enjoyable evening in the company of a lovely group of PhD students and young post-docs discussing life the universe and everything – and trying not to feel my age!

At the close of my 3-day crash course in SMLM, I certainly felt much better-informed and very much inspired by the amazing work being done by this small but enthusiastic community. It is certainly an area of research I will continue to follow closely – perhaps a trip to Bordeaux is on the cards for next year!

1. Quantitative imaging of membrane lipid order in cells and organisms Dylan M Owen,    Carles Rentero, Astrid Magenau, Ahmed Abu-Siniyeh & Katharina Gaus Nature Protocols 7, 24–35 (2012) doi:10.1038/nprot.2011.419

2. Direct stochastic optical reconstruction microscopy with standard fluorescent probes Sebastian van de Linde, Anna Löschberger, Teresa Klein, Meike Heidbreder, Steve Wolter, Mike Heilemann & Markus Sauer Nature Protocols 6, 991–1009 (2011) doi:10.1038/nprot.2011.336

The last couple of months have been busy for the Nature Protocols editors, with Mel and I both travelling a fair amount. The end of September saw me heading off to Istanbul, Turkey for the EMBO workshop on “Decoding neural circuit structure and function”. I had been thinking a little warmth at the end of September would be a welcome change, but ironically I think it was actually warmer in London! And we didn’t really need all the rain to encourage us to attend sessions, given the excellent line up.

I don’t have the space to discuss all the talks at great length, and it was also encouraging to see so much unpublished data being presented, which I must not share. But here are my highlights.

The first talk of the meeting was by Juergen Knoblich, and it was great to hear about his current projects, using Drosophila genetics to understand cell cycle exit and quiescence plus the contribution of changing the balance of asymmetric versus symmetric divisions in development of various disorders. It was also good to hear that his group are doing more work on the brain organoids, whose creation has already been explained in their group’s recent Nature Protocols article. I was intrigued that a member of the audience asked about the ethical implications of such organoids – it was a question I asked myself whilst editing our article.

I enjoyed learning about behavioural assays using the larval zebrafish from Florian Engert. It was amazing to see what such tiny organisms are capable of. Scott Waddell’s talk was focused to resolving how an animal decides to do the most appropriate thing at a particular moment, using Drosophila as his model system. This question came up as the main research question being addressed in several speaker’s talks.

Another fascinating talk was by Leslie Vosshall on “Sensory cues driving host-seeking behavior in the dengue vector mosquito Aedes aegypti”. Leslie’s groups’ research should help address whether there is any truth in the various old wives tales concerning whether particular factors increase a person’s attractiveness to mosquitos. I spoke to some other researchers about Leslie’s talk and they are confident Leslie will be able to improve the repertoire of molecular biology research tools available for the study of Aedes aegypti. So, it is worth keeping an eye on what Leslie is up to.

The final talk of the conference was by Gero Miesenböck. I very much enjoyed the pictures of the T-maze apparatus his group uses to perform mass behavioural assays in Drosophila.

In addition to all the fabulous talks there were stimulating poster sessions. I particularly liked the poster by Deniz Atasoy from Medipol University, Istanbul, on a Genetically encoded synaptic marker for electron microscopy (GESEM) that he developed. This poster was awarded the Nature Protocols poster prize, going to the poster with the best protocol behind it. Special mention should also go to Xuefan Gao from the Max Planck Institute for Developmental Biology in Tubingen, whose poster on AVEXIS, a protein-protein interaction screen assay, was also very methodological in slant.

Do let us know if you are organising a conference and would like to have a Nature Protocols poster prize as we are always looking out for opportunities to sponsor such prizes.

We also enjoyed conference dinners at Boğaziçi Üniversitesi and on a boat on the Bosphorus – so it wasn’t all work! The conference organisers, Arzu Celik, Nilay Yapici and Hernan Lopez-Schier, deserve a special thank you for being so welcoming and organising such a good program. Istanbul is a beautiful city and well worth a visit.

Last thursday I went to an inspiring talk given by Michael Levitt, joint winner of the 2013 Nobel prize for chemistry. It was the 2014 Sir Ernst Chain Lecture at Imperial College, London.
Starting with a project using lysozyme (where the co-ordinates for the computer input came from a ball and stick model and were typed onto punch cards) and early computer simulations of protein folding, to his more recent work on modelling ribosomes and eukaryote chaperonins, he presented a small slice of the amazing work that he and his collaborators have done. What was equally evident was the phenomenal advances in technology and computational power over the last 40 years.
He is currently holding a chair in Cancer Research at Stanford, and spoke a little about the work on humanised antibodies that he did with Cary Queen  at Protein Design Labs (a company that formed in 1987, is now PDL biopharma  and produced patents that underpinned the development of drugs like Herceptin,and Avastin).

He included a slide providing advice to the young:
Be passionate
Be persistent
Be original
Be kind and good (or, at least, act kind and good…)

He thanked the Nobel Committee for Chemistry for, amongst other things, considering awarding a prize for a method rather than a solution; a sentiment especially pleasing to the editors of Nature Protocols!

Some of the slides were similar to those published here.
In 2003, he prepared a series of video talklets to form a web-based class on Computational Structural Biology. These are available on-line; and I plan to listen to as many of these as I can this coming weekend! Structural Biology 228 | Computational Structural Biology

About a month ago, I attended the ‘Beyond the Genome (BTG): Cancer Genomics’ meeting in Boston—my second conference as Chief Editor of Nature Protocols (my first was the 2014 ARR meeting at the University of Sussex). The BTG meeting grabbed my attention for several reasons; firstly, the topic was more-or-less within my comfort zone; secondly, there was a heavy focus on bioinformatics (a rapidly developing and important field); and thirdly, the line-up was fantastic. Fortunately, it was a small meeting so I was able to pin down several of the key speakers, including Fred Alt, Gad Getz, Peter Park, Nuria Lopez-Bigas, Mike Schatz, Nils Gehlenborg, and Rosalie Sears, and poke my head into some of their ‘labs’ (offices).

Given the bioinformatics focus of the meeting, it is perhaps unsurprising that many of them spoke about the need for easy-to-follow instructions for biologists branching out into bioinformatics and using complex computational tools for the first time. As Peter Park pointed out to me, “biologists and bioinformaticists speak different languages, and few journals seem to bridge this gap”. As it happens, some of our most popular protocols (e.g. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources, which has been cited almost 4,000 times) fit this bill perfectly, providing clear, concise, step-by-step instructions for using popular bioinformatics tools and software packages. Written by bioinformaticists, reviewed by biologists and bioinformaticists, and edited by (ex)-biologists, these protocols help researchers without a bioinformatics background to analyse their data themselves. Given the popularity of these protocols and the growing importance of bioinformatics within the biomedical sciences, this seems like an obvious area for expansion of the journal (so watch this space!)

With more than 40 talks over three days, a comprehensive overview of the BTG meeting is out of the question, so instead I will highlight a few of my favourites. On the first day, Gad Getz opened the talks with a discussion of MutSig, software developed by his group for identifying driver genes (by analysing lists of mutations and territory covered during sequencing) and building models of the background mutation processes that occur during tumour formation. Jan Korbel stepped up next, explaining the system he has set up for constructing maps of unbalanced SVs based on whole-genome DNA sequencing data. At the end of the day, Fred Alt spoke passionately about his recent work on high-throughput genomic translocation sequencing (HTGTS) strategies to identify translocations that arise from fixed DSBs, as well as sites of endogenous genomic DSBs.

The next morning, Rosalie Sears gave an interesting talk on the use of 3D tissue bioprinters to generate tumour tissue, as well as normal healthy tissue. Printer ‘ink’ 1 (consisting of endothelial cells, fibroblasts, and immune cells) is added first; printer ‘ink’ 2 (cancer cells) is then added to look at tissue distribution and assess cell interactions. Unfortunately, only a few labs have access to such advanced technology but this could change over the next 5-10 years as the set-up cost inevitably drops. Later that day, Lynda Chin talked about data she has collected using ChromHMM, a computational tool set up by Ernst and Kellis for predicting chromatin ‘states’ (based on combinations of chromatin marks) and characterizing their biological functions.

On the third and final day, Mike Schatz kicked off proceedings with a ‘bioinformatics challenge’ relating to single-cell CNV analysis. The challenge has become a regular feature of ‘Beyond the Genome’, encouraging students, postdocs, and analysts in the audience to get “down and dirty with data to solve an informatics problem as quickly as possible” (as Mike puts it). The task opened up to the floor this year (“should you chose to accept it”) was to resolve the population structure of a collection of cells, establishing which cells were in the same clone and, for each clone, which was the most highly amplified oncogene. Schatz provided data for simulated single-cell sequencing of a population of 9 cells with 250k reads per cell (all for chromosome 1 (not whole genome) at 0.5x coverage). He also provided a list of 100 candidate genes. As this coverage is too sparse to identify point mutations, the genome must be divided into “bins” (with 50-100 reads/bin) before mapping the reads and counting reads/bin. Copy number variations in a single cell can be identified as bins with significantly fewer or significantly more reads, and the population structure can be examined by finding cells with the same patterns of bin counts (see our Protocol on this).

After an initial flurry of activity as people rose to the challenge, the audience settled down to hear Nils Gehlenborg talk about the applications of StratomeX, an interactive visualization tool he developed in the Park lab to compare differences in molecular profiles across patient sets. Then, just after lunch, Schatz announced the winner of the bioinformatics challenge; René Böttcher, a PhD student in Guido Jenster’s lab in the Erasmus Medical Center in Rotterdam, was the first to solve the challenge in just over 1 hour (congratulations, René!). As the closing remarks drew nearer, Peter Park gave a fantastic talk on the different single-cell sequencing approaches, with tips on comparing data obtained using different techniques (e.g. GC bias with MDA sequencing, better read-depth stability at large scales with MALBEC than with MDA, more consistent depth at small scales with MDA, etc.). Shortly afterwards, a sea of smiling faces left the auditorium, with many promises to return next year.

It was my first visit to the Emerald Isle, and most definitely worth it. However short, my three-day permanence in Belfast to attend The 15^th International Meeting on Human Genome Variation and Complex Genome Analysis (HGV2014) was fruitful and thoroughly enjoyable.

I flew from London Gatwick to Belfast International Airport on an early morning flight on September 17^th, never a good start of the day; not for me at least, given my long-term experience with low-cost flights that leave REALLY early in the morning bound for my native Sicily from London, the city I have emigrated to, and where Nature Protocols is based. You’ve got to suffer to go Sicily, it seems — and be mildly uncomfortable to go to Ireland.

Well, the discomfort did not last long. As soon as I climbed onto a cab just outside Belfast Airport, the friendly cabbie exclaimed “Culloden? It’s the best hotel in Northern Ireland, sir. Five stars, you know?” Culloden Estate and Spa was to double as the venue of the conference and my hotel accommodation. That review by an undoubtedly knowledgeable local sure felt nice to hear. Time to relax on the back seat of the car and take in the scenery on that drizzly morning as the cab drove for about 35 minutes through the Irish countryside, skirting downtown Belfast, before arriving at Holywood, the Belfast suburb where Culloden Estate and Spa is located. The castle-resembling hotel is immersed in quite spectacular greenery, both within and without the hotel grounds, and the hilly locale overlooks Belfast Lough, the deep inlet of the Irish Sea at the end of which is located Belfast, with its harbor. When the cab pulls over by the main entrance of the Culloden, a man in impeccable grey tail-coat and top hat opens the car door for me with a smile. Wow, that’s not the kind of treatment the average former chemistry researcher is accustomed to…

Time to check in, undo my suitcase in my room, and walk to the event room to register for the conference. There, I am handed my name badge “Baldo Lucchese – McMillan Publishers” by Sinead Lawlor, the über-efficient overseer of the conference organization. She explains to me that the conference will be attended by 126 participants, ten of them exhibitors (I think I am included among those ten), and there will be 54 research poster presentations. A pretty manageable conference size-wise from my standpoint. Among the participants are also three researchers who have written protocols for our journal, Dr. Ido Amit of the Weizmann Institute, the corresponding author of High-throughput chromatin immunoprecipitation for genome-wide mapping of in vivo protein-DNA interaction and epigenetic states, and doctors Yves Moreau and Thierry Voet of the University of Leuven, co-authors of Microarray analysis of copy number variation in single cells. Always nice to find one’s footing in that sense at a conference.

Time to dive into the talks. We are welcomed to HGV2014 by this year’s conference organizer, Dr. Mark Lawler of Queen’s University Belfast, who has also been instrumental to my attendance. As he will explain to me the next day, he moved from Dublin’s Trinity College — Mark is actually a native Dubliner (don’t they say “Dub”?) — to Belfast’s Queen’s University barely a year and a half ago, so it has been quite the struggle for him to organize HGV2014 in his new hometown. You surely wouldn’t have guessed from the results, however. I couldn’t be happier with my accommodation, the conference will progress smoothly and the talks will prove excellent.

HGV2014 is articulated into seven sessions distributed over three days, which will include a total of 36 talks and three round-table discussions. Of the 33 speakers from academia and the three from industry, the vast majority hail from either the British Isles or the US, although there are also a total of eight speakers from Canada, Italy, Belgium, Germany, and Israel.

The first of talk of the first session, “Interpreting the Human Variome”, is given by Dr. Pui-Yan Kwok of the University of California San Francisco, a member of the organizing committee and a veteran organizer of this conference. The talk, “Structural Variation in the Human Genome”, seizes my technique-oriented, Nature-Protocolly (warped?) mind. One of Dr. Kwok’s group research focuses is the study of structural variations of the human genome, variations like gene deletions, insertions, duplications, inversions and translocations. Many of these features are associated with particular diseases and disease phenotypes, but they are often hard to identify and define using whole-genome analyses, which rely on the mapping on short DNA reads ‘chopped’ from the full length genomic DNA and matched to a reference genome. This approach can provide ambiguous information when it comes to identifying, for instance, the number of times a gene is repeated in sequence along a stretch of genomic DNA, a rather important parameter to measure in some research and clinical contexts.

Dr. Kwok’s laboratory, in collaboration with BioNano Genomics Inc., a company based in San Diego, California, has developed “Genome Mapping in Nanochannels”, a technique that is particularly suited to identifying structural variations in the genome. In this approach, instead of being reduced in size, long stretches of human DNA are first nicked at several positions on only one DNA strand using a nicking endonuclease expected to nick about 12 times every 100,000 bases. These nicks are then repaired using fluorescent nucleotides and the full-length DNA molecules are then uncoiled and forced to pass through narrow parallel nanochannels, in which only one DNA molecule can fit at a time. The DNA molecules are then photographed as they move along the nanochannels. Given that the nucleotide sequence recognized by the nicking enzyme is known, that a reference genome exists, and that one obtains clear images of where the fluorescent nucleotides have been inserted along the genomic DNA stretch, a researcher can now, for instance, literally count on a photograph the number of repeats of a particular gene. Using this approach, Pui-Yan Kwok’s research group believe to have closed some of the sequence gaps in the human genome, its ‘grey areas’ of ambiguous sequence assignment that are probably due to the presence of structural variations.

The following Session II, “Tracing and Targeting the Tractable Cancer Genome”, was in principle a bit too focused on clinical research from the standpoint of Nature Protocols remit; nevertheless, it did rouse my curiosity. The lecture by Dr. Lillian Siu of the University of Toronto was particularly thought-provoking from my layman’s point of view. Lillian Siu’s research focuses on the study of inter-patient and intra-tumor genomic heterogeneity in the context of cancer. It has been known for years that cancer patients with specific genetic signatures tend to respond (or not respond) to specific drug treatments in a somewhat predictable fashion. Such genetic heterogeneity is the basis of the so-called personalized medicine approach to treatment. Dr. Siu sketched for the audience the clinical trial designs that take into account genetic heterogeneity. At one end is the ‘umbrella trial’, in which all participants share the same tumor type (for instance lung cancer), according to histology results, and they are assigned to different drug treatments based on their relevant genetic aberrations. At the other end is the ‘basket trial’, in which patients with different cancers based on histology are pooled together into treatment groups based only on their genetic aberrations, irrespective of histological evidence. Finally, she described the N-of-1 trial design, which consists of a comparison of the results of two different treatments applied to the same patient: in this trial design, time-to-progression in a patient on a genotype-matched treatment is compared to the same parameter in the same patient when he/she was on a prior, and presumably non-genotype-matched, treatment.

At the end of this talk, a calculatedly provocative question from a member of the audience rang: “So, are randomized, controlled trials a thing of the past?” Well, given my background as former associate editor at Nature Reviews Nephrology and Nature Reviews Gastroenterology and Hepatology, this question made me sit up: aren’t they the gold standard for medical trials? Lillian Siu clearly did not want to be drawn into sweeping generalizations, but she explained that, in a genotype-matched drug clinical trial, tumor responses may be sufficiently significant and objective for conditional drug approval of the drug to be granted in some cases. In this context, she thought that, prospectively, randomized trials are likely to become less and less prevalent, given how exhausting they can be for research resources as well as for patients. It sure was a treat to witness this exchange…

The next day’s morning session was entitled “Phenomes, Genomes and Archaeomes: Solving the Conundrums”. I have had a small obsession for studies on ancient DNA genomics for a while, so it came to no surprise to me that I found the talk “Ancient Population Genomics: Do It All or Not At All” by Dr. Dan Bradley of Trinity College Dublin, particularly exciting. As Dan Bradley reported, a key difficulty when working with ancient DNA is that when collecting DNA from a typical ancient human bone sample, only about 1% of it is DNA from the original owner of the bone, the rest is leftover from various contaminations. He and his research group have used bioinformatics tools that enable researchers to sift through the sequencing data from ancient DNA that does not need to be particularly pure to infer which sequences pertain the individual to whom the biological sample belonged and which are, instead, due to contaminants.

Dan Bradley reported results from his group and collaborator’s research that help shed some light onto the population and cultural changes that Europe underwent between the Mesolithic through to the Iron age, via the Neolithic and Bronze age. One of the overarching questions his group has been trying to address is whether age-defining technological/cultural innovations were exchanged ‘osmotically’ between populations or whether such dramatic changes, for instance from a hunter-gatherer culture to an agricultural one, are associated with new human populations displacing the previously resident ones. Although their data on this subject appears to be a bit of a mixed bag, evidence seems to indicate that in most cases an age-defining technological or cultural shift also coincides with a population replacing or pushing aside another. Well, it does make sense in a sad sort of way.

Session IV “Answering the Global Genomics Challenge — Time to Step up to the Plate”, late morning on September 18^th included talks that focused on ongoing international efforts to sharing genetic data across research centers and across countries to share evidence about genetic mutations and how they may be associated with the onset of, or the predisposition to, disease. Dr. Anthony Brookes of the University of Leicester, among other projects, recounted the design and purpose of Cafe Variome project. This project in particular stuck to my mind because the previous day I had had the chance to talk about it with Dr. Owen Lancaster from Brookes’ lab, who was presenting a poster describing Cafe Variome.

As Owen also clarified for me, Cafe Variome tries to shift the basic nature of the problem of accessing data on mutations and phenotypes that, despite their high potential usefulness, are currently not being openly shared due to legal, ethical or competitive reasons. Cafe Variome tries to clear this roadblock by providing a platform whereby the existence rather than the substance of the data is made accessible to subscribers. Once these discovery ‘hits’ are achieved, the platform facilitates exchange of the data in the form the most suits the relationship between data requestor and data owner: data summaries, data displays, data links, data owner contact details, or a form for data automated data request and subsequent provision.

Presently Cafe Variome, which is hosted by the University of Leicester, supports networks of rare disease diagnostic laboratories or research consortia that share an interest in certain causative genes or diseases, know and trust each other to different degrees, and wish to have a full picture of what records and information exists across the collaborating network. Six such federations are currently trialing the platform, and, Owen explained, one of them will be shortly opening up their content also for public discovery. Well, fascinating stuff for someone like myself who is a bit obsessed with data sharing and privacy, particularly when it comes to genetic make-up. Sooner or later I should write a post on that too…

Session V, “Improving our Health: Time to Get Personal”, was particularly engaging. In the first talk, “Personalised Cancer Medicine: Are We There Yet?”, Mark Lawler described the efforts and purpose of the European Alliance for Personalised Medicine, of which he is a member, an international association that aims to promote personalized medicine and its delivery in the health systems of European countries and to develop patient-centered European translational research platforms. It was clear how much enthusiasm and personal stake Mark has in promoting personalized medicine in the context of cancer treatment, but from the last talk of the session it was also clear, at least to me, that he does not take himself overly seriously, and he is quite open to discussion.

The last ‘proper’ talk of this session, aside from being quite entertaining, was rather unusual in that it was given by Professor Timothy Caulfield, a researcher in the area of health law, biotechnology policy and bioethics. The title of talk, “Marketing the Myth of Personalized Prevention in the Age of Genomics”, already conveys a lot of the tone of this presentation. Timothy Caulfield is a bit of a skeptic of personalized medicine, and he started his lecture by thanking Mark Lawler for inviting him to talk at the conference despite his stance and, presumably, he implied, as a way to kick-start a lively discussion. Caulfield does not believe that the prevention of common diseases is likely to be affected by personalized medicine. Progress in genetic research, he argues, has been hailed as heralding a ‘revolution’ for decades now. But this revolution has yet to materialize. He is also rather offended by what he calls ‘science-ploitation’, via which for-profit companies, even those commercializing beauty creams, for instance, claim that their products can be targeted and tailor-made to suit the personal needs of customers based on their genetic make-up. A number of sleek commercial ads with portentous ‘scientific’ claims succeeded each other on the screen at various times as Caulfield gave his presentation.

The core of his objecting to the promotion of, for instance, widespread genetic testing in the healthy population in the wake of the personalized medicine ‘revolution’ lies in the research that points to the fact being made aware of a predisposition to a particular condition or disease does not change the behavior of individuals to any significant or measurable level. Focus on genetic testing and personalized approach when it comes to public health policies, he argues, shifts responsibility from the political and social level to the individual, when it is proven that only ‘general’ policy decisions can spur changes in social attitudes and, ultimately, change the behavior of individuals. To drive home the point about science-ploitation of the concept of personalized medicine, Caulfield recounted how he had had his genome sequenced by an American commercial company. Caulfield shared with the audience some of the results he had obtained, which meant that he had a slightly elevated predisposition, compared to the average, to a few medical conditions. The ‘bespoke’ advice that he received from the commercial company was to exercise, drink in moderation and not smoke… So much for the personalized prevention regime; point made, I’d say. Science-ploitation… That’s a word that I’ll end up using a lot, I’m guessing, sorry Professor Caulfield.

This session was capped by a round table discussion entitled “Prime Time for Personalised Medicine”, which had a TV talk-show format, in which the chair, conference co-organizer Dr. Stephen Chanock of the National Cancer Institute, Maryland, moderated the discussion of a five-membered panel that included also Timothy Caulfield, Mark Lawler, and Lillian Siu. Of course different points of view and opinions were shared during the discussion, but the panel ultimately agreed that the sensationalization and mis-representation by the general interest and popular press and by commercial companies of the results and implications of genetic research are a significant problem for the scientific community. However understandable sometimes, these tendencies could ultimately harm genetic and genomic research itself. A tentative solution proposed by several of the panelists and a few members of the audience was for scientists to become more actively involved in the public discourse about genomic and genetic research, so as to offer additional means for the public to correctly frame this discussion and interpret the significance of research findings. Proposals were made that scientists should try, for instance, to make themselves more savvy and effective in the use of social media like Twitter, although some confusion immediately ensued this proposal as some panelists and members of the audience couldn’t initially agree on the character limit of twitter feeds. Nevertheless, it was an encouraging start all in all, given that the matter was eventually correctly settled: that limit is 140.

An excellent conclusion of the day’s lectures, before the gala dinner of the conference, which took place at the Titanic Signature Building, an attraction that opened to the public in 2012 and is located in the section of Belfast harbor where the RMS Titanic was built. This building, which is exactly as tall as the Titanic’s highest tip, hosts a multi-storey, multimedia museum themed on the building and ultimate sinking of the Titanic. Us conference participants were taken on a guided tour of the museum that chronologically followed the Titanic (mis)adventure and that culminated in a viewing of the striking underwater footage of the wreck of the Titanic shot from a deep-sea submersible in the 2004 expedition undertaken by marine explorer Robert Ballard together with the National Oceanic and Atmospheric Administration (NOAA). Naturally, a very fancy and very satisfying dinner followed, made particularly enjoyable by light conversations with my table mates, researchers from Spain, the Philippines via California, Britain, and Sweden.

The last day of the conference was dedicated to sessions VI, “Understanding the Evolving Genome”, and VII, “Next-Gen ‘Omics and the Actioanable Genome”. It was also the day of two Sponsor Presentations, one of which was by BioNano Genomics Inc.’s Dr. Han Cao, “Towards the True Contiguity Resolving the “Dark Matter” of Genome”, which covered also the technique already introduced on the first day of the conference by Dr. Pui-Yan Kwok for Genome Mapping in Nanochannels, and that BioNano is currently applying also to the study of non-human genomes. As mentioned, pretty fascinating stuff from the point of view of a technique-biased scientific reporter.

Talking about techniques, the last day of HGV2014 was also dedicated to giving awards to the best posters. In advance of my attendance of the conference, Nature Protocols had proposed to award a one-year online personal subscription to the journal to the presenter of the poster describing the most interesting technique, and Mark Lawler had been immediately enthusiastic and supportive of the idea. As I walked around speaking with poster presenters, I also got to chat with Nature Protocols authors Ido Amit and Thierry Voet. They were possibly being nice, but they both told me that they enjoyed their experience as authors of our journal, and they considered Nature Protocols a very useful resource. It may not be statistically significant with just two subjects, but they both ended up putting more work than they had anticipated into their Protocols, but they felt it was entirely worth it. A quiet sigh of relief on my part welcomed the conclusion of their reflection. Surprisingly, both of my interlocutors, to whom I spoke separately, by the way, also felt that it would be of great help if Protocol authors could submit video tutorials alongside their manuscripts. Fact is, however, that authors can already do so, and a minority of the Protocols we publish do come with supplementary information in the form of videos. Clearly, we must do more to make our authors more aware of this possibility.

Going back to the posters, maybe unsurprisingly, Nature Protocols, in its yours truly incarnation, decided to award the prize for the poster describing the most interesting technique to Dr. Angel Mak, a post-doc in Puy-Yan Kwok’s University of California San Francisco laboratory, for the poster entitled “De novo genome assembly and structural variations detection by genome mapping in nanochannel arrays”. Of course, the technique described in the poster is none other than Genome Mapping in Nanochannels, already described in Dr. Kwok’s lecture two days earlier. My sincere congratulations on your research work Angel! But I had a wonderful time looking up all the posters and talking to several of the presenters. Very exciting work being presented by each poster, and thank you to all the researchers I spoke to, none of whom let transpire any disappointment at the dumbness of some of my questions.

It was Friday after 4 pm by the time I announced the winner of Nature Protocols’s prize, and it was time for me to catch a cab to go to the airport. I had to give a miss to the Irish Night — Whiskey Tasting Experience and Culture Night Performance Including Broadway Acclaimed Actor Eilin O Dea, organized for 5.30 pm that evening. A London night was beckoning for me; not that I had anything special planned, in fact I had nothing at all planned, but even with my relatively early flight from Belfast, I did not reach home till 11 pm that night. Sadly, I’m too old for anything more lively than that. And hey, now I’ve got an excuse to go back to Belfast and complete the Northern Irish experience…

Thanks a lot Mark and thanks a lot HGV2014 participants for the excellent time all around!

My three days at the European Symposium on Biological and Organic Chemistry (ESBOC) did not start in the most auspicious way. Or, again, maybe they did. Well, Friday the 17^th, the day of my departure, is a day of bad luck in Italy, much like Friday 13^th is in many other countries (it may not sound like it given my name, but I am indeed Italian), and my stopover at Birmingham New Street station to catch my connection to Newtown (Powys), Wales, certainly got my heart pumping.

To make a long story short, my apparently comfortable fifteen-minute leeway between my arrival from London Euston and my departure to (seemingly unknown in Birmingham) Newtown got eaten away by a mostly fruitless search for ‘my’ platform in a station, which, I later found out, is undergoing significant redevelopment — and is not very passenger-friendly. After a few minutes’ queue to reach the information desk, I got sent by the guy behind it to “platform 5b”, when I probably had something like seven minutes left to spare. After about five minutes of frantic soul-searching while pacing on a platform that just didn’t seem right, and that was at once platform 5, platform 5a and platform 5b, I grabbed my trusty trolley by the neck, ran up the stairs to the main concourse, then to the closest display panel, and finally down the stairs to platform 6b, as a train moved slowly past it. Was it my train? Was it pulling in? Was it pulling out? Well, suffice to say that, much to my relief, I made it to Newtown on time to catch the minibus meant to take all ESBOC participants arriving by train to the conference venue at Gregynog, a relatively isolated location about 8 km of narrow, windy road away from the town.

View of Gregynog. Courtesy of Dr. James Redman.

Gregynog… It is actually a beautiful country house surrounded by 750 acres of (beautiful, it behooves to stress) gardens and woods sitting right in the middle of Wales. It was donated to the University of Wales in 1960 by its owner, the late Miss Margaret Davies, as an arts center. As I started looking for my room, a friendly and slightly surprised member of staff exclaimed, “Room G2? It’s one of our two best rooms sir!” Wow, time to let my hair down, if I hadn’t just had it cut rather short, that is. The room was actually very nice and comfy, and I had something like half an hour to unpack before the conference reception and presentation.

This year’s annual conference was the 47^th of the series, as this symposium was first organized here at Gregynog in 1967 by Professor Cedric Hassall of University College, Swansea. At the time, it was called Gregynog Natural Products Symposium, a name changed to European Symposium In Bio-Organic Chemistry in 1971, to become the present-day European Symposium on Biological and Organic Chemistry only in 2011. This year’s chair, Professor Kai Johnsson of EPFL Lausanne, Switzerland, could actually not be present, as his wife is expecting a baby imminently, so the role of hosts was entrusted to the capable hands of the Chairman of the Steering Committee, Professor Tim Bugg of the University of Warwick, and of the Treasurer and Secretary, Dr. James Redman of Cardiff University.

Cover of the program of the 1967 Gregynog Natural Products Symposium.Courtesy of Dr. James Redman.

The title of this year’s symposium was “Chemical Probes for Cellular Processes”, a subject that elicited an excellent response of corporate and non-corporate sponsors and, according to Professor Bugg, the most international attendance of the symposium to date. This year’s ESBOC had 60 participants from eight different countries affiliated to both academic institutions and industry. The program included 18 lectures by invited speakers, ten of them plenary and two ‘named’, and it also included a 12-strong poster session. Among the scheduled speakers were Nature Protocols’s own authors Ben Cravatt of the Scripps Research Institute, Edward Tate of Imperial College London, and Carsten Schultz of EMBL Heidelberg. All the talks, which included lectures by ‘industry’ speakers Dr. Ivan Correa of New England Biolabs and Dr. Keith Wood of Promega, were up my alley, so to speak, as they were generally given by chemists who applied their skills to attempt to answer biological questions, exactly my research background.

Participants of the 1969 Gregynog Natural Products Symposium. Cedric Hassall is the second person on the left seated. Courtesy of Professor Timothy Bugg.

It wasn’t just that I understood the talks in their entirety, which is undoubtedly a big plus, but I actually really enjoyed them. The symposium was small enough that no talks needed to be scheduled at the same time, so I was able to attend all of them. The lectures spanned subjects like applying bioluminescence to the study of intracellular interactions or the imaging of fatty acids, activity-based protein profiling, phage selection of peptides with different bio-relevant properties, the synthesis of riboswitches to control gene expression, the expansion of the SNAP-tag tool box, and fluorescence-based approaches to investigate nucleic acid structure. Talking about activity-based protein profiling, unfortunately Professor Ben Cravatt, who was supposed to give the first day’s Royal Society of Chemistry Bio-Organic Group Lecture entitled “Activity-based proteomics: applications for enzyme and inhibitor discovery”, could not be present, due to a family commitment, but he was replaced by post-doc Ken Hsu from his lab, who, despite the short notice and an 8-hour jetlag — Scripps is in San Diego, California — gave a wonderful talk on the use of activity-based protein profiling on serine hydrolases for the discovery of bioactive lipid networks by chemoproteomics and metabolomics.

The next day’s ‘marquee’ talk, the Cedric Hassall Lecture (“In vivo selective optical imaging of tiny tumors to rationally designed activatable fuorescence probes”), was to be given instead by Professor Yasutero Urano, of the University of Tokyo. Except that Yasutero was not the speaker’s first name. As he initiated his talk, Professor Urano pointed out that his name is actually YasuterU, and went on to speculate that the tendency of his European colleagues to spell it with an “O” must be due to an understandable mental association between himself and Elvis CostellO. Well, to be honest, I did not see much of a physical resemblance between Professor Urano and Elvis Costello, not least because the former is obviously much younger. The association was made clearer, however, by the thunderous applause that greeted the end of Urano’s lecture. A really impressive talk, even for an outsider like myself.

Professor Urano had described his laboratory’s work on synthesizing and testing probes that become fluorescent only when taken up by tumor cells, a strategy that would prospectively enhance surgeons’ ability to literally see cancerous tissues when operating. Urano’s research group had used two main approaches to achieve their goal. In one, pH-sensitive fluorescent probes are fused to an antibody specific to membrane receptors that are highly expressed on the surface of tumor cells. Upon endocytosis, the low-pH environment of the cell lysosome causes activation of the probe, which thus becomes fluorescent. In the second, the probe is fluorescently inactive as long as it remains bound to an appended peptide group, which can however be cleaved by GGT, a peptidase highly expressed on the surface of tumor cells. Upon cleavage of the peptide bond, the newly fluorescent and highly hydrophobic probe concentrates first on the cell membrane, and, eventually, inside the cell, to highlight that cell’s unhealthy state. What did I say? Really impressive.

As ESBOC drew towards its end, I even found out how Gregynog is pronounced correctly. Two competing schools of thought seemed to take shape on the matter at the conference. According to participants with Welsh connections, the pronunciation in southern Wales would be something like Greg-EYE-nog, whereas people in northern Wales may actually pronounce it Greg-E-nog. Unfortunately Gregynog is almost in the dead center of Wales… Mystery solved on Saturday night, however, when we ESBOC participants were entertained by the charming music of Welsh harp player and folk singer Siân James, clearly a reliable source on all things Welsh. To my untrained ear, she pronounced the locale “Greg-e-nog”, making a slight clicking sound with her tongue when she uttered the second and third g’s of the word.

What can I say? My experience at ESBOC was excellent all around. The place was fantastic, the talks outstanding, the participants friendly and chatty, and my ‘contacts’, Professor Bugg and Dr. Redman, always helpful. Even the food was terrific. Word on the street was that Gregynog had recently hired a new German chef, and everyone was raving about him. Ok, I am Italian, but I have to admit that he really knew his stuff. On Sunday the weather too smiled on us, with a gloriously sunny day; too bad that we were about to leave and that strolling around the grounds had been scheduled for the day before. Oh well, not bad for a conference two train and one minibus ride away that started on a Friday the seventeenth…

Well, the last bit of important information concerns next year’s ESBOC at Gregynog: ESBOC 2014 will take place on 16–18 May, and it will be organized by next year’s scientific chair, Dr. José Luis Mascareñas of the Universidade de Santiago de Compostela, in Spain. The title of that conference will be “Biological Applications of Supramolecular Chemistry”. Make time to go, if you can.

So I’m back… Well, I have actually been back for a little while already, as this year’s Mathematical and Statistical Aspects in Molecular Biology (MASAMB) meeting was held last April 11th and 12th.

Mission accomplished, it is fair to say. The idea was for me to acquaint myself face-to-face with research areas — bioinformatics and statistical genetics — which Nature Protocols has always covered, and in which it hopes to be even more active in the near future. For sure, over a day and a half I had the opportunity to attend a total of 25 presentations divided into five sessions: statistical bioinformatics, computational cell biology, next-generation sequencing, systems biology, and evolution. I will not claim to have understood everything I heard, but all presentations were stimulating and thought-provoking. Given my background in ‘wet’ chemistry and biochemistry, I guess it was no surprise that I found it easier to follow the biological side of the talks than the parts that dealt with mathematical and computational models, but I am now much more familiar with the landscape in this research area.

My attendance of MASAMB, as I discovered on site, was primarily made possible by the engaging and amiable host of this year’s MASAMB, Dr. Michael Stumpf of Imperial College, via the intercession of my email contact, Dr. Louise English. During one of the poster sessions, Michael explained to me that one of the main goals of MASAMB is to provide PhD students and post-docs with a workshop-like venue in which to present their own research in an environment that is more ‘intimate’ and less intimidating than the average meeting. Students and post-docs are those most encouraged to present their work, Michael added, and most of the conference speakers belong to this category.

Besides the scientific quality of the presentations, I was quite impressed with how well they were timed and organized. Each talk was to last 20 minutes, including eventual questions from the audience, and not a single presentation out of 25 went long, while the switch between speakers always ran smoothly and quickly. I found this to be quite the impressive feat, both in terms of the technical prowess of the meeting organizers and of the scholarliness of the young — and one would assume generally relatively inexperienced — speakers.

This year’s MASAMB conference attendance was about 110, toward the high-end of the average, but it still felt quite ‘cozy’ for participants and reporters alike (well, for the only reporter, me). Speakers were mostly from UK institutions (e.g., Imperial College, UCL, University of Glasgow, University of Warwick, University of Bristol, Cancer Research UK, Brunel University, University of Manchester, University of Sheffield and the University of Reading), but there was also a significant representation of researchers from other European countries, including Cyprus (University of Cyprus), Germany (EMBL Heidelberg), Austria (Center for Integrative Bioinformatics and the University of Veterinary Medicine), Switzerland (ETH-Zürich), Poland (Polish Academy of Sciences), and Finland (Aalto University).

If I were a young scientist being trained in computational biology or bioinformatics in a European institution, I would try my best to attend MASAMB, and apply to either give an oral presentation or present a poster on my own research. Talking about posters, the poster count for this year’s conference was 35, which, according to Michael Stumpf’s concluding remarks, included “not a single stinker!” The high quality of the pool made it all the more impressive for the winners of this year’s best poster competition: Ann Babtie, Dominic Smith and Phoebe Jones from Imperial College for “A moment expansion approach for stochastic simulation and inference” and Agnes Jonas from the University of Veterinary Medicine of Vienna for “Modelling allele frequency trajectories of experimental evolution with fruit flies”. On presenting the awards, Stumpf remarked how pleasantly impressed he was that three of the four recipients were women, even though the vast majority of entrants were men. Well, you heard it, if you’re not just a young scientist, but also a woman, it’s time to do your best to attend the upcoming MASAMBs and extend the flattering gender-slanted tradition.

Well, attending MASAMB XXIII was an excellent experience, which would not have been nearly as pleasant or useful if it weren’t for the current and former members of the Stumpf laboratory. Aside from Michael himself, I had the opportunity to meet and converse (about science and everything else) with research fellows Tina Toni and Sarah Filippi, post-doc Juliane Liepe, graduate students Ann Babtie, Adam McLean and Delphine Rolando, and former Stumpf group member (now a post-doc at the University of Cyprus) Kamil Erguler. I sincerely thank them for their invaluable help and for making me feel very welcome. I feel Nature Protocols and I have now an ‘in’ into the world of bioinformatics research, and I look forward to receiving news and feedback on how Nature Protocols can be of more help to researchers in this field — right Juliane?

One last bit of information: the general preference is for the yearly MASAMB meeting to take place in the UK for two consecutive years, then somewhere else in Europe, before returning to these shores. Tentatively, MASAMB 2014 will take place at the University of Sheffield, a venue that was preferred by this year’s participants to the other two candidates, Warsaw and UCL. Stay tuned…