Presented by Team Paris Bettencourt 2020
Amandine Maire1, Anu Susan Kurian1, Chetan Kumar Velumurugan1, Nicolas Levrier1, Nikola Zarevski1, Valerie March1, Xavier Olessa-Daragon1, Ariel Lindner2, Jake Wintermute2, Radoslaw Ejsmont2, Alexis Casas2, Darshak Bhatt2
1Student Team Member, 2Team Mentor
1. Sample and Sequence the Human Skin Microbiome
Our first objective, pursued as part of the Quaranskin project, is to study the impact of environmental and behavioral factors on the skin microbiome and to provide a new database to study its composition in the context of reduced social and environmental interactions.
2. Design tools to engineer the bacterium S. epidermidis
Our second objective is to make S. epidermidis an efficient synthetic biology chassis that can be used to monitor the population dynamics of the skin microbiome. This in order to maintain its equilibrium and to avoid pathologies induced by dysbiosis.
In the context of COVID-19 pandemic, we were, as most of the other iGEM teams confined at home.
As this situation was unprecedented, we were wondering if the lockdown could have an impact on human health and more specifically on the composition of our skin microbiome.
We met some dermatologists as Stéphanie Leclerc-Mercier. She pointed out the fact that the new sanitary measures and hygiene habits imposed by the pandemic were a real issue for people with eczema symptoms since they cannot wash their hands as often as healthy people. This discussion drew our interest for dysbiosis induced pathologies and ways to treat them using synthetic biology.
Our team personal values led us to create a project who enters in the framework of Open and Citizen Science. Especially during the lockdown which forced us to be physically isolated of each other, we wanted to find a way to connect people through science.
1. Study the Skin Microbiome
Human skin microbiome sampling is a challenge in itself since it implies reaching out to a large cohort and collecting human being derived samples. In the context of a pandemic other constraints are added because of social distancing measures.
2. Engineer the Skin Microbiome
1. Quaranskin
Quaranskin is a study involving the collection of skin microbiome samples during the COVID-19 pandemic and observing the impact of environmental factors on the skin microbiome.
2. EpiFlex, EpiGlow, EpiGrow
These three projects aims to develop tools to make S. epidermidis a good chassis for Synthetic biology.
What is the Skin Microbiome?
The human skin microbiome is a vast and very large ecosystem of microorganisms that occupy the human skin at the level of the hypodermis, dermis, and epidermis. It is very numerous and very diverse, a real petri dish hidden in plain sight.
How the Skin Microbiome plays a role in the skin health?
The human skin microbiome is very tightly linked to the health of its host in numerous ways. First of all the microorganisms of the skin microbiome prevent the colonization of the skin by pathological microorganisms, and help to train the immune system to make it more prepared to face pathogens. It also directly involved in various pathologies, like atopic dermatitis, where its overall diversity is reduced and Staphylococcus aureus is over represented.
Why studying the composition of the Skin Microbiome?
Quaranskin, a combination of quarantine and skin, is a project based on the collection and analysis of skin microbiome samples, collected from participants across Europe.
We aim to understand if there are correlations between behavioral characteristics that involve activity, hygiene and human interaction, and the diversity and composition of skin microbes at four body sites.
Study Pipeline
Participants recruitment
Emails are sent to all the members of our institution, the CRI, and all the european iGEMers, by focusing on people form countries where confinement or social distanciation are set up. The total number of participants expected is 70.
Participants enrollment
To be involved in the study each participants has to fill in a participation form and link to it a signed and dated consent form.
A link is sent to them allowing them to create a account on the OpenHumans platform in order to furnish them an ID code which we use to keep anonymity
Participants action
Once they are officially enroll in the study, we send to the participants by mail a kit containing all tools needed to sample microbiome from 4 body sites and to send them back to us, and by email a link to answer an online questionnaire asking questions covering 4 main topics : The intrinsic characteristic (age, sexe, nationality...), the hygiene habits, the level of confinement and the skin disorder appeared since February 2020.
Microbiome sequencing
Once we receive the microbiome samples we send them directly to an external company, Genewiz. They’ll extract bacterial DNA from the samples, amplify the V3-V4 regions of the 16S RNA gene, and then sequence the amplicons.
Statistical analysis
After having analyzed the composition and diversity of each microbiome we’ll link these results to the answer to the questionnaire to finally find some correlations between some microbiome compositions and some characteristics of the lifestyle or some skin disorder
Data Analysis
1. Diversity analysis by index of hygiene, personal information, level of restriction
The microbiomes in the generated database are grouped by index value in each of the 3 categories. By setting two indices, we can study the impact of the third element on the diversity of the microbiome
2. Environmental factors which influence proportion of Staphylococcus
We define a proportion threshold, then we identify all the people who present a population of Staphylococcus beyond this threshold. We finally look for parameters common to these individuals,
3. Researching existing microbiome composition among our data set
We want to compare a typical composition of eczematic microbiome found in literature, with our data
4. Analysis of data based on common symptoms
When a significant number of people present the same symptom, independently of the environment and lifestyle, we want to make a synthesis of the typical composition of the microbiome for this symptom.
Ethical consideration
As Quaranskin is a collection of data extracted from human derived samples (skin microbiome) and personal information (answer to the questionnaire), it’s important to learn about the ethical rules that govern research involving human being in Europe in order to respect the protection of the participants in our study.
In France, Research Involving Human Being (RIPH) has to be approved and framed by the Committees for the Protection of Persons (CPP).
We have submitted to the ethics committee a complete file presenting our study in detail. This file consisted mainly of a research protocol and all the information documents for the study participants. Even though we already recruit participant and set up all the logistic aspect of the study, we are still waiting for their approval to collect and analyse samples.
Contribution to the scientific community
Biological engineering allowed us to develop solutions for our objectives.
Purpose
We aim to sense and modulate populations dynamics of the skin microbiome in order to help maintain its equilibrium and avoid dysbiosis induced pathologies. This is where we envision the role of synthetic biology in the probiotic arena.
More precisely, we thought about engineering S. epidermidis in order to control overgrowth of S. aureus which can induce eczema symptoms.
S. epidermidis
S. epidermidis represents approximately 90% of the aerobic skin flora, and about 5% of the overall skin microbiome species. It is a non-motile gram-positive coccus, and a facultative anaerobe. Its mainly mutualistic behavior makes it a very good candidate to become a vector for sensors or ways to modulate the skin microbiome.
Research Focus
Three essential stages we want to optimize to help engineering S. epidermidis :
