Technology and Research Mendeley Masterclass

©Tom Atkinson 2013 - www.r3digital.co.uk
©Tom Atkinson 2013

Last month we saw another edition of the global extravaganza that is Social Media Week. This time around there were over 1000 events and 25,000 attendees in 8 cities around the globe. The theme for this year was “Open & Connected” which is pretty much a perfect fit for the Mendeley philosophy. So we thought it would be great to host an event in the London SMW Hub about how technology is changing the way we conduct and fund research, how researchers interact, discover content and share their findings, as well as how the non-academic public can get involved and make a real different through citizen science initiatives.

Our Masterclass was streamed live and proved to be one of the most popular events of the week, with hundreds of people tuning in and sending their own questions.

Mendeley Co-founder and President Jan Reichelt kicked off the series of lightning presentations by explaining how Mendeley can help researchers organise their papers, but also how it went far beyond that. “Research is an inherently social activity, and Mendeley is an environment starting with productivity going over into collaboration, and that also crucially captures the social context going on around that research.”

Rachel Greene from JoVE challenged researchers to “stop reading and start watching,” explaining how the majority of the time scientists failed to accurately replicate the findings of key studies. She believes that technologies such as the one used in their peer-reviewed Journal of Visualized Experiments are much more suited for that purpose than traditional print, and can therefore dramatically increase reproducibility and the pace of scientific discovery.

“In the past everything was recorded on paper, but current science is very digital,” says IJsbrand Jan Aalbersberg from Elsevier’s Article of the Future project, which aims to improve scientific communication in all its rich facets. “All the records are digital, all the capturing of scientific data is digital, and the communication of that information of course is also digital. However the traditional publishers have not yet adapted to that, what they usually do is flatten the multidimensional, rich research that an author has created into a two-dimensional paper of text and images.” He gave insight into some tantalizing possibilities, including the ability to run variations of some experiments – in computer science for example – within the parameters of the article itself, making it a living, evolving piece of collaborative research.

Nicolai Humphreys from The Lancet told of how the meaning of the journal’s name came from the fact that “A lancet can be an arched window to let light in and can also be a sharp surgical instrument to cut out the dross” and upon founding the journal in 1823 Thomas Wakley stated his intention that the publication should serve both those functions. Fast-forward nearly 200 years and Nicolai is part of the team that is using technology to cut out the dross and make academic publishing more dynamic and cutting edge.

Emma Cooper described the journey that took their digital amusements company Team Cooper to developing a Facebook game in conjunction with The Sainsbury Laboratory to help harness the brainpower of citizen scientists to tackle Ash Dieback disease. Quoting Dr Dan MacLean, who approached them about building the game with their data, “humans are smart and humorous, and we love games.” The key to the success of Fraxinus is the human ability to recognise patterns, and this proved really addictive with players (over 38,000 in the first month), who spend 20 minutes on average playing the game, where the average tends to be around 5-10 minutes.

That is what Robert Simpson from citizen science web portal Zooniverse calls “cognitive surplus,” which describes the vast amount of time that we collectively spend on activities such as watching TV. “The human race spends 16 years every hour playing Angry Birds every hour. There’s a lot of brainpower out there and what we try to do is take that brainpower and make it more useful to researchers.” The team at Zooniverse works with researchers to design sites that take their data and presents it into a format that will let the crowd help them to achieve their objectives. In the case of Snapshot Serengeti, for example, this meant classifying the millions of pictures taken over 2 years by camera traps in Tanzania to provide new insight into wildlife dynamics.

“These days with modern technology Citizen Science is becoming a fresh new hot subject in science,” says Margaret Gold of Citizen Cyberlab, which is leveraging the web, mobile phones and other tools and platforms to enable crowd-sourced scientific research. “We give people across the globe an interactive means to either help with the collection of data or the processing of data, pattern recognition and so forth, and all this makes a very genuine contribution towards science.”

Dr Rayna Stamboliyska, a Research Fellow and Digital Content Coordinator at the Centre for Research and Interdisciplinarity in Paris, believes that technology can be used to bring research into primary schools, and that “we can change the world many kids at a time.” In these programs, PhD fellows work with school children to develop research projects, leveraging and incorporating various technologies and social media. “This not only engages them in the STEM curricula at a young age, but it’s a really gender neutral policy, so we’re addressing the problem of having so few women in science.”

But ground-breaking research often comes across the stumbling block that is lack of funding, and this is where Liz Wald from Indiegogo believes that crowdfunding can help scientists. “it’s really about getting rid of gatekeepers, knocking down barriers and taking ideas right to the crowd,” she said as she went through a few of the projects that were crowdfunded through Indiegogo, such as Kite Patch (a patch that lets people avoid mosquito bites) and uBiome (where you sent off swabs of your bacteria to them so that they could let you know more about yourself and also help the wider project to sequence the Microbiome). The message was that people will not only fund cool and useful gadgets, but all forms of science as long as you tell a good story.

If you missed it on the day don’t worry, all the presentations are on the Mendeley YouTube Channel, so you can watch them any time and let us know what you think! There are also some cool pictures of the day available on our Flickr page, we had a great time and thanks again to all our speakers and community!

 

 

 

JoVE Guest Blog Post – Visualising Scientific Experiments

JoVE October blog

This is the first in a series of guest posts from JoVE, the Journal of Visualized Experiments. Each month we’ll be featuring a different peer-reviewed video article with insights from their team. Like Mendeley, JoVE is using technology to make science more open, and we were really happy to have their Director of Marketing Rachel Greene join us at Social Media Week London for the Mendeley Masterclass on How Technology is Changing Research. You can watch the video of her presentation, talking about how visualising experiments enhance reproducibility on the Mendeley YouTube channel, and as usual let us know what you think in the comments below!

MALDI-TOF MS, an Adaptable Method for Protein Characterization, Visualized in a JoVE-Chemistry Video Article

(J. Vis. Exp. (79) e50635, doi:10.3791/50635 (2013))

By Val Buntrock, Ph.D.

Journal Development Editor, JoVE

A recent video-article published in JoVE, the Journal of Visualized Experiments, by a research group at the Centre National de la Racherche Scientifique (CNRS) captures the process of analyzing intact proteins using mass spectrometry (MS). In their video article, Signor et al. demonstrate how to accurately measure large proteins using matrix assisted laser-desorption ionization time-of-flight (MALDI-TOF) MS. Often, when describing MALDI-TOF MS procedures in text, essential information is omitted, leading to poor reproducibility. Part of a new trend in publishing, this video demonstration records the subtleties and nuances of this complex technique. Employing proper technique and variable consideration, this research group identifies an intact, large protein (> 100 kDa) with high sensitivity using a small amount (0.5 pmoles) of protein sample. Using these video instructions, research groups around the globe can modify this flexible technique to identify an infinite number of large proteins.

Phosphoregulation

Characterizing proteins is important for determining the current state of the protein, which has severe implications to several biological processes. The significance of proteins switching between active and inactive forms via protein kinase phosphorylation events has been recognized and applied to cellular and molecular research for several decades. Researchers have gone on to show that protein folding, as determined by phosphorylation, either exposes or protects structural motifs that serve as binding sites for effector molecules. Further, the binding between protein and effector molecule controls protein function. Therefore, the initial protein phosphorylation event regulates the activity level of the protein.

Protein activity or function plays a role in switching on or off a large number of cellular processes, such as cell communication and cell replication. As structural biologists identify a growing number of disease states related to malfunctioning protein modifications and subsequent de-regulation, understanding and identifying the differences between the two states of the protein (active or inactive) has become a priority.

Protein Characterization

A simple, fast, and common method of determining the presence or absence of phosphorylation in proteins is by determining their mass using mass spectrometry (MS). MS ionizes the molecule of interest, generating a charged species, and measures its mass-to-charge or m/z ratio.  The m/z ratio is determined by the isotopic distribution of each element present, meaning that each molecule or protein has its own unique isotopic pattern or fingerprint.

Two MS techniques are typically used to ionize heavy and labile biomolecules, such as proteins: electrospray ionization (ESI MS) and matrix assisted laser-desorption ionization time-of-flight (MALDI-TOF MS). ESI MS analysis requires dissolution of the sample in a pure solvent for direct ionization from the solution mixture. MALDI-TOF MS utilizes a co-crystallization method wherein the protein is crystallized with an ultraviolet (UV) absorbing organic species. This organic molecule is referred to as the matrix molecule or substance.

While ESI MS is more sensitive and accurate, the instrument compatible solvents or buffers typically contain significant amounts of substances, such detergents and salts, which interfere with the desired protein pattern. Additionally, ESI MS data is more difficult to interpret given that ESI MS spectra are riddled with multiple overlapping charge states from a single protein. A more gentle technique, MALDI-TOF MS produces fewer multiply-charged species, leading to a much cleaner spectra that is easier to analyze. This is especially true for larger biomolecules, such as proteins, which can fragment into numerous multiply charged species using ESI MS. For these reasons, MALDI-TOF MS is the preferred technique for protein analysis.

Optimizing MALDI-TOF MS Technique

Matrix

Purity at every stage of MALDI-TOF MS analysis is crucial to obtaining the highest quality MS spectra or protein fingerprint. For this reason, Signor et al. provide detailed instructions for how to effectively 1) clean the MALDI plate that holds the matrix and protein of interest and 2) purify the matrix substances using standard recrystallization techniques. Further, they employ two different matrix systems to compare which one yields the best results for the protein of interest. A single matrix and a mixed matrix system are used, demonstrating the influence of the matrix on the resulting spectra. In their work, Signor et al. found that the mixed matrix system yielded a higher signal to noise and a greater sensitivity than the single matrix system.

Deposition Method

The deposition method is another technique variable that impacts the quality of MALDI-TOF MS results. The two most commonly employed deposition methods are the droplet and thin layer method. Using a droplet technique, a mixture of the protein analyte and matrix solution is “dropped” onto the target substrate, and the solvent is evaporated, yielding a crystalline mixture of the matrix and protein. Slightly more controlled, the thin layer technique is composed of layers of matrix sandwiching the protein analyte layer. While the droplet method suffers from poor resolution and an inability to observe larger proteins (> 100 kDa), the thin layer deposition yields a protein fingerprint for large proteins, sharper peaks, and a higher signal to noise.

As protein analysis becomes a more vital component of studying protein modifications, mastering protein characterization techniques is increasingly important. In this video-article, Signor et al. provide a detailed overview of the steps involved in utilizing MALDI-TOF MS to analyze proteins. They also provide essential considerations and modifications to guide beginners and experts alike through tailoring this powerful technique to study different target proteins. Shown in video format, the necessary level of details, such as how to properly perform multiple deposition methods, is captured and relayed to the viewer for increased transparency.