Botanical Observation

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In 1729, Jean-Jacques d’Ortus de Mairan (1678-1771) laid the foundations of modern chronobiology. A French interdisciplinary researcher, he  designed an experiment demonstrating the existence of a circadian rhythm in plants, potentially deriving from an endogenous clock. These observations and experiments led to the development of chronobiology. I have translated below the original article from 1729 presented by his colleague Mr. Marchant.

De Mairan, J.J.O. 1729. Observation Botanique, Histoire de l’Academie Royale des Sciences, Paris, p. 35.

We know that the “Sensitive” [Mimosa pudica] is a heliotrope [i.e., “sleep in plants”], meaning that the branches and leaves are always directed toward the greatest amount of light, and we know moreover that this property is common to other plants, but it has a more particular one. It is sensitive to the sun or the day, the leaves and their pedicle fold up at sunset, similarly as when we touch, or we shake the plant.

But Mr. de Mairan observed that this phenomenon does not require that the plant be outdoors or exposed to the sun.  The phenomenon is slightly less prominent when it happens in a dark environment, but  the plant expands significantly during the day and folds up or shrinks regularly in the night. The experiment was done during the summer and was repeated well. The Sensitive feel the sun without seeing it at all. It may have a probable connection with the ability of a lot of sick people to differentiate day and night from their bed. It would be interesting to test whether other plants, whose leaves or flowers expand during the day and shrink during the night, conserve this property in dark environments like the Sensitive.

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Figure 1: Experimental Design, light-dark versus constant dark setup.

It would be curious if we could test this property in a hotter or colder oven (incubator), a day or a night that the plant feels, or if we could reverse the day and night and apprehend the order of the phenomena of the real day and the real night, etc. But the ordinary schedule of Mr. de Mairan does not allow him to push these experiments further, and he simply invites botanists and physicists [natural philosophers] to find themselves other things  [experiments/hypotheses] to follow [study/research]. The progress of true physics [i.e., science, natural philosophy], which is experimental, can be only very slow.

article original

Figure 2: Original manuscript (in French)

Comments on “Botanical Observation”

This research, performed by de Mairan and presented by Marchant, contains the  seeds of modern chronobiology. With this short paper/observation de Mairan and Marchant suggested the existence of an endogenous biological rhythm. He showed that light is not necessary for the oscillations of Mimosa pudica‘s leaves and branches along the day/night cycle; these oscillations persist in the absence of light. However, de Mairan and Marchant were quite careful with their interpretation of the ability of plants to measure time, as they could not rule out other potential confounding factors: temperature cycles, light leaks, or changes in other meteorological parameters. In addition, they already suggested the connection with temperature (compensation/entrainment) using an incubator in a proposed experiment (which was later performed by others), and they suggested a modern experimental design with day/night inversion.

 “It may have a probable connection with the ability of sick people to differentiate day and night from their bed.”

Then, in the discussion of the results, de Mairan and Marchant drew an interesting parallel with sick people who can feel the day or night from their bed without actually seeing the light. With this simple comment de Mairan and Marchant insinuated that humans may have an endogenous clock as well.

 “The experiment was done during summer and was repeated well.”

The authors were concerned about the repeatability of the phenomena, a prerequisite of both the scientific method and modern statistical thinking. However, the paper does not provide detailed “materials and methods,” so we cannot know if “well repeated” experiments implies that the experiment was done a few times for a day or two, or if the same plants were studied over many days. We have no information on the time resolution (how often the researcher checked the plants). Indeed, de Mairan did not detect that the plants opened up their leaves a little earlier each day––a “free-running” rhythm with a period slightly shorter than 24 hours, which is strong evidence that the rhythm is endogenous.

“He simply invites botanists and physicists [natural philosophers] to find themselves other things to follow.”

As de Mairan’s schedule was packed with many other fields of research (e.g., astronomy), and his responsibilities at the Academie Royale des Sciences, he did not want to invest his time in writing and publishing a paper on a “mere plant.”  Thus his experiment was reported by his colleague Marchant. Similarly, de Mairan invites other scientists (“botanists and physicists”) to follow up on these experiments. Many scientists from different backgrounds, such as mathematics, bio-physics, bio-informatics/computational biology, chemistry, medicine, and more, accepted this invitation and enriched the development of chronobiology.

Finally, Marchant and de Mairan concluded the essay by saying that true science is experimental and a very slow process. Indeed, nearly 300 years after his observation, the field of chronobiology is still in progress, and three of its main contributors, namely Jeffrey Hall, Michael Rosbash, and Michael Young, received the Nobel Prize in 2017 for their characterization of the molecular circadian clock. The field of chronobiology will lead to a better understanding of rhythms governing our behavior and physiology.

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A perfect timing is crucial

Time is money! a good timing is always crucial in an economic entity as a company or a Start-up. In such system, you have to coordinate many processes, such as your resources, your supply chain, your production with the market needs. Being able to anticipate the change in demand and consequently adapting your offer will enable you to have an advantage over your competitors and achieve growth and eventually the survival of your company.

The_Persistence_of_Memory

In a biological system it is very similar. Timing is the key to coordinate many physiological processes. You have resources coming from food, fat storage, and you need to properly allocate these resources when you need them at the right time and the right place. Our body has an internal timing system called the circadian clock, which provides us the ability to anticipate environmental changes. This regulatory network is intricated with our metabolism in order to regulate a large variety of processes such as feeding-fasting cycles, sleep wake cycles, and more. In the lab of Gad Asher we study the cross-talk between the circadian clock and the metabolism at the molecular level to understand the fundamental properties of our daily-rhythms.  We want to understand what affects this temporal variation and how our health can benefit from any perturbations in our dietary income or in our exercise schedule. I’m currently working as a data scientist and I’m using statistical modelling and large-scale gene expression and metabolites analysis in order to study these processes.

BeerDeCoded: Exploring the beer metagenome

Originally published as a F1000 Blog article

Jonathan Sobel shares his scientific quest to understand beer at a molecular level

A citizen science project carried out by the Hackuarium Association investigated the genome of various beers. The results of this work were published as as a Data Note on F1000Research. Jonthan Sobel explains what the thinking was behind this project and what they found. 

Beer is a fantastic beverage produced through a fermentation process and widely consumed around the world. It has inspired many generations of scientists and citizens. For instance, the famous student T-Test was initially developed for the beer industry, and has now become a popular statistical test for biologists. Again, James Joule was a brewer, who discovered the first law of thermodynamics with his brewing equipment. Many of us enjoy a good beer with our friends, and like to discover new ones.

Beer, an inspiration to generations

At Hackuarium, we chose beer to discuss the challenges and opportunities of DNA sequencing with fellow citizen scientists. The knowledge that we are acquiring could be of interest for breweries and microbreweries to develop new products.

Beer microorganisms

We wanted to detect different microorganisms in the beer ecosystem. Comparing different beers, allowed us to assess their similarities and their specificities, to see if there was a terroir – regional environmental factors that affect the properties of the final product – for beer, similarly to wine and cheese making. We thought this would trigger a discussion with a wider audience on the ethical issues regarding DNA sequencing data, while showing what we could learn about the product.

Creative solutions

Hackuarium, the bio-hacker space founded in 2014 by Luc Henry, was of paramount importance in the development of this project and bringing the team together. The team had experts from various backgrounds, including biologists, bioinformaticians, designers, a social community manager and business developer, met at the association.

By working in this association, we had greater freedom in choosing the direction of our project than in a company or in academia. We could virtually work on anything, providing that it was in agreement with our ethical charter and the law.

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When we set out on the project we had no money, so we had to find creative solutions to finance the project. In 2015, a kickstarter campaign led by Gianpaolo Rando provided us with the resources to generate a first dataset that we are now publishing as proof of concept in F1000Research.

The beer ecosystem

We produced a descriptive dataset of the fungal diversity referred to as the ITS region in 39 beers from 5 countries. Our preliminary analysis, revealed that the beer ecosystem is richer than expected in terms of fungal species.

In all the beers in our dataset, we found several Saccharomyces species, as well as  several species specific to one beer that could potentially represent their genetic identity, i.e., an internal fingerprint of authenticity.

Some ITS species could just be contaminants introduced during the beer making process, which could affect the final product quality, but that remains to be investigated.

Improving public understanding of sequencing

BeerDeCoded is an ambassador project about the DNA sequencing of a mass consumption product. Many have an idea about the beer production process or have a favourite beer, so using a familiar product makes it easier to communicate about molecular biology and sequencing techniques.

We are currently working with Berenice Batut from the Galaxy training network to train future generations of bioinformaticians with this dataset. We are also in discussion with other citizen science groups to export this project to other cities, to generate and gather more beer related data to expand our knowledge base.

Short Bio

Jonathan Sobel PhD pursued his master’s in a mucosal immunity lab at Lausanne university hospital, CHUV, where he studied the effect of lipoxin A4 on endometriosis at the protein level. Then, he did his Ph.D. in the computational systems biology lab at EPFL where he studied the interplay between metabolism and the circadian cycle in mouse liver, using next generation sequencing approaches. He joined the Regazzi lab at the university of Lausanne in 2017 as a post-doc in bioinformatics to study beta-cell maturation. Side to his academic work, Jonathan was involved in Hackuarium, a bio-hacker space in Renens, where he did science popularization.

A social community manager in a BioHacker space

In a biohacker space such as Hackuarium, the main force is the group of people. Their competencies and their motivation will drastically impact the success of their projects. The board of the association usually takes care of some operational considerations such as event planning, infrastructure improvements or treasury. One central role is the social community manager. His purpose is to introduce new members and to find the needed human resources for each project. He follows the progress, and he encourages members to publish their results and populate the wiki with their findings. He is as well responsible for giving physical and digital access to the community, and he helps to shape the external communication of the association. All these tasks are crucial to attract new members and projects. Also, this role is of paramount importance for the sustainability of the community. This role may be the first to require a professional person and therefore a salary that ensures the motivation of the social community manager. If the community manager fails in his tasks, the image of the community in its whole is impacted.

In an old project called “Quantitative Anthropology”, we performed a community analysis of our Slack team. This analysis has been done during the first year of Hackuarium and demonstrated the volume of exchanges between the community members.

hackuarium_network_2015

This network visualized with Cytoscape, show the most active members as well as the central role of the community manager, at that time our friend Shalf. The nodes represent the people, and the purple edges show the volume of exchange.

Depending on the size of the association, the treasury, and the amount of work, the board might include more professionals. But before reaching this stage, the association’s size should reach a critical mass of about 200 members. Today hackuarium has about 110 members with around 15 active projects. Our ability to grow our community and our capacity to fulfill each role needed on the board will determine the sustainability of Hackuarium in the following years.

BOSC session of the ECCB/ISMB 2017

As the lucky recipient of an Open Bioinformatics Foundation (OBF) travel grant, I had the chance to attend to my first Bio-informatics Open Source Conference (BOSC) in Prague the 21 and 22 July 2017.

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During the event, I discovered an amazing community of scientists and developers involved in the field of bioinformatics, with a strong open source mindset. “Sharing is caring” and I can tell these guys care a lot! The first day was quite technical with several talks about projects developed during the code fest that happen just prior to the conference. I had the opportunity to discover the FAIR principles (Findability, Accessibility, Interoperability, and Reproducibility) of open data, and several tools aimed at simplifying bioinformatics workflow sharing, visualizing and production. These teams triggered my curiosity towards the Common Workflow Language (CWL) and data standards, notably RABIX, GA4GH and nextflow. Several talks presented very useful tools such as YAMP (Yet Another Metagenomic Pipline!) or MiltiQC for next generation sequencing quality control, and Open MS 2.0 for mass-spectrometry data analysis. One important topic of the day was the reproducibility of bioinformatics piplines and several talks were addressing this question with various approaches, such as containers (Dockers, BioContainers), GNU Guix or package repository such as BioConda.

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On the second day, I had the chance to present our BeerDeCoded project in the Citizen Science session of the BOSC. I had the first slot in the morning with an audience of nearly 250 attendees. The beer topic is kind of holy in a geek environment. I had the pleasure to share several important message regarding science conducted outside of academia or industry, in a community laboratory space like Hackuarium. I put some emphasis about science communication between fields and outside of our institutional scientific community. As experts, we have the responsibility to make our knowledge and our researches accessible to a wide audience, and this is exactly our goal with BeerDeCoded and Hackuarium. In addition, I could announce the official release of our first results based on the metagenomic analysis of 39 beer samples. I was able to show our preliminary analysis. The BOSC community was really enthusiastic about the project and attendees tweeted quite a lot about it.

In addition, I had some very interesting questions about the interest of breweries in BeerDeCoded, the potential fear of companies that citizen scientist decode their proprietary yeast strain or about the data integration of sequencing with GC/MS in order to study small molecules present in our beer data-set. Moreover, this talk will potentially trigger new collaborations with with Bérénice Batut from the Galaxy training networkGalaxy is an open source, web-based platform for data intensive biomedical research. The Galaxy platform regroups a collection of bioinformatics tools and workflow that can be run without coding knowledge. This program is widely used by biologists to analyze their next generation sequencing data. BeerDeCoded will benefit from this collaboration with a specific instance of Galaxy to make the beer metagenomics accessible to anyone.

Later during this second day, I was impressed by several other talks. One of the greatest initiative is the work of the H3ABioNet, which aim at training bioinformaticians in Africa. I discovered the Journal of open source software (JOSS) that facilitate the publication of bioinformatics software. Then, BioThings SDK and Wikidata presented their API and their knowledge base that allows retrieving efficiently some annotations of biological data. This day was as well the occasion to discuss about data sharing of human data (wearable, clinical, etc.) in order to improve precision medicine and the ethical implication. In addition, second-hand data usage and the problem of re-digitalization of published data in a non-machine readable format was evoked. Finally, Nick Loman gave the closing keynote presentation at BOSC. He gave a great talk about virus outburst surveillance using the Oxford nanopore minION sequencing technology, using two examples, namely Ebola outburst in Africa in 2015 and the Zika virus in Brazil.

In summary my first BOSC experience was very intense and highly interesting. I met with great scientists and developers and I learned about the newest open source software/library/API and practices in this field. I would like to thank once again the BOF committee for allowing me to join this great event and to give me the opportunity to present Hackuarium and the BeerDeCoded project.