7th Biotechnocentre theme day – June 17, 2022

Researchers in biosciences and life chemistry met "face-to-face" for the Biotechnocentre's thematic day on "Exposome and Epigenetics: how does the environment play with our genes?" ". Renowned speakers declined the different facets of the exposome: physical or chemical exposure or exposure to different pathogens, stress, diet, social inequalities... They also highlighted the impact of the exposome on the environment and on our health, which can have different consequences depending on gender, age, genetic heritage and on its regulation by reversible epigenetic modifications.

In Cellulo and In Vivo Comparison of 3 helper lipids for Lipid Nanoparticle Formulation of mRNA

LNPs are a leading class of mRNA delivery systems. LNPs are made of an ionizable lipid, a polyethyleneglycol (PEG)-lipid conjugate and helper lipids. The success of LNPs is due to proprietary ionizable lipids and appropriate helper lipids.

Using a benchmark lipid (D-Lin-MC3) researchers compared the ability of three helper lipids to transfect dendritic cells in cellulo and in vivo. Studies revealed that the choice of helper lipid does not influence the transfection efficiency of immortalized cells but, LNPs prepared with DOPE (dioleylphosphatidylethanolamine) and β-sitosterol were more efficient for mRNA transfection in murine dendritic cells than LNPs containing DSPC (distearoylphosphatidylcholine).

This higher potency of DOPE and β-sitosterol LNPs for mRNA expression was also evident in vivo but only at low mRNA doses.

References of the article published in Nanomaterials:
Ayoub Medjmedj, Albert Ngalle-Loth, Rudy Clemnçon, Josef Hamacek, Chantal Pichon and Federico Perche
In Cellulo and In Vivo Comparison of Cholesterol, Beta-Sitosterol and Dioleylphosphatidylethanolamine for Lipid Nanoparticle Formulation of mRNA
Nanomaterials 2022, 12(14), 2446; https://doi.org/10.3390/nano12142446

A unique biosensor able to detect as low as 10 nM bioavailable copper based on whole-cell eukaryotic Saccharomyces cerevisiae

Cooper in a micronutrient essential to life, its lack induces neurological and blood disorders. It is extensively used in industry, in particular in the batteries of electric cars, but also as a fertilizer and fungicide. However, it is toxic at high concentrations, and is considered as a critical emerging pollutant. Copper detection in water constitutes a major societal and environmental issue.

Currently, copper concentrations are monitored by sophisticated analytical methods requiring time, expansive equipments and deep expertises. Moreover, these technics quantify total copper present in a sample and not copper interacting with living organisms.

Researchers of CBM developed a new and atypical device able to detect copper in a very sensitive and easy way. Their biosensor is based on whole-cell eukaryotic living Saccharomyces cerevisiae, allowing detection of bioavailable copper. It is a ratiometric biosensor, measuring the ratio between (i) a constitutively expressed fluorescent protein and (ii) another fluorescent protein whose expression is directly correlated with copper concentrations as its expression is in under the control of CUP1 promoter, a well-known promoter in Saccharomyces.

By genetic engineering, researchers created many different variants to optimize the response of our biosensor. Their best biosensor is able to detect as low as 10 nM of copper in a linear range from 10-3 to 10-8 M, much better features compared to other currently reported whole cell copper biosensors. This biosensor was also validated on “real” samples: detected concentrations are totally in agreement with manufacturers’ values.

Reference of the article :
Bojan Zunar, Christine Mosrin, Hélène Bénédetti, Béatrice Vallée
Re-engineering of CUP1 promoter and Cup2/Ace1 transactivator to convert Saccharomyces cerevisiae into a whole-cell eukaryotic biosensor capable of detecting 10 nM of bioavailable copper
Biosensors and Bioelectronics 214 (2022) 114502

The article was reported by the CNRS Institute of Chemistry on its website and in its letter "En direct des labos".

 

Chantal Pichon has been appointed Senior Member under the Innovation Chair of the Institut universitaire de France

Chantal Pichon, Professor at the University of Orléans practicing at the Molecular Biophysics Center, is one of the 164 appointed to the Institut Universitaire de France (IUF) by the Minister of Higher Education and Research.

Chantal Pichon has been appointed Senior Member under the Innovation Chair of the Institut universitaire de France from October 1, 2022, for a period of 5 years.

The Institut Universitaire de France's mission is to promote the development of high-level research in universities and to strengthen interdisciplinarity.

List of Winners

Research interests

C. Pichon is conducting interdisciplinary projects based on chemistry and molecular and cell biology with a crosstalk between basic and applied researches. C. Pichon’s main research activities are dedicated mainly to the use of nucleic acids as therapeutics. These last years, she is particularly interested in messenger RNAs vaccines and therapeutics. She is developing innovative formulations for their delivery for various applications: mucosal vaccination, cell-based therapies and protein replacement therapy. C. Pichon has patented mRNA bioproduction technology based on a tailor-made yeast-based mRNA factory platform, a complete shift of paradigm compared to in vitro production and a revolutionary new use of yeast. She envisions to build an economically sustainable biotechnology process for production of high-quality mRNA therapeutics opening their use in different applications. Social disparities between and within European countries and all over the world are negatively associated with access to new biopharmaceuticals as mRNAs.