Micro-RNA, a serious alternative to chemical fertilizers and pesticides

NATURAL. What we thought was useless could still serve and even have an extremely positive role. It is the discovery made by the Laboratory of research in plant sciences (LRSV, mixed unit CNRS / University of Toulouse) on the role of microRNAs published in Nature in 2015 . This scientific breakthrough is now leading to the development of a start-up that is of interest to two venture capital companies. Which have just contributed 4 million euros to develop the fertilizers and pesticides of the future.

Present in the cells of most living beings, the microRNAs produce, at least among the plant s, natural peptides that can temporarily regulate the expression of genes of interest that can act for example on germination, flowering, fruiting, but also on the defenses against attacks of pathogens. " MicroRNAs are natural tools that cells use to regulate the quantity of certain particularly important messenger RNAs, and thus through them the expression of most of the key genes for plant development ", explains Thomas Laurent, general manager of Micropep .

An additional supply of peptides improves the performance of the plant

NUCLEOTIDES. In all plants, the genesis of a microRNA begins with a maturation phase during which a long sequence ranging from 300 to 3000 nucleotides is cut to obtain a small sequence of only 21 nucleotides: a microRNA. mature". It is this mature microRNA that then makes it possible to regulate the expression of the gene that corresponds to it. Until now, it was thought that apart from the mature microRNA, the rest of the long initial sequence was useless. However, the LRSV team has detected peptides (small proteins) it calls "miPEP". It then demonstrates that an additional supply of these peptides makes it possible to increase the amount of the corresponding microRNA, and consequently to temporarily influence the genes controlled by this microRNA.

Jean-Philippe Combier, co-discoverer of the miPEP. © La dépêche du midi

This fundamental discovery is rapidly supported and protected by the Society for Acceleration and Transfer of Technology (SATT) of Toulouse, which invests nearly 500,000 euros in patents and proofs of concepts between 2013 and 2015. The potential of the discovery is indeed immense: the plants possess between 200 and 1000 microRNAs which are all directly or indirectly involved in the major metabolic functions of plants, such as growth or their capacity of resistance. In another article Toulouse researchers show for example that an additional supply of miPEP172 (targeting microRNA # 172) accelerates the nodulation of soybean, a beneficial symbiosis between the roots of the plant and plants. bacteria allowing this legume to better utilize nitrogen from the air to grow. Similar evidence of efficacy has been made for mycorrhizal symbiosis, another beneficial association between fungi and roots that facilitates plant uptake of soil organic matter. By targeting the right microRNAs, the miPEPs could thus be used to significantly improve the plants' natural abilities.

A new generation of environmentally friendly organic inputs

REVOLUTION. The idea becomes obvious: to develop a new generation of biological inputs from these miPEPs to reduce the use of chemicals traditionally used in agriculture . It became the goal of Micropep Technologie, the company created in April 2016 by Thomas Laurent and the two main researchers behind the discovery, Jean-Philippe Combier and Dominique Lauressergues, with the help of SATT Toulouse Tech Transfer. " This is a breakthrough technology that could really revolutionize plant biology and agriculture says Thomas Laurent. miPEPs are molecules of natural origin, easily degradable in environment, extremely specific, and with a unique and extremely precise mode of action: the temporary regulation of genes via microRNAs.We are thus at the crossroads between plant genetics, which is generally at the heart of the selection work of seeds, and that of biological inputs aimed at significantly reducing the use of pesticides in agrochemicals.And although we speak of genetics, we do not touch the DNA of plants ". [19659002] If the fundraising of Tuesday, March 6 has been necessary, it is because the development work is still important and we will have to invest a lot more and hire researchers. First work: to continue to identify new peptides by associating for each cultivated plant the peptides and the genes that they influence. It is therefore a "library" of molecules that must be patiently built. Then we will have to work on the development of formulated products that can be easily used by farmers. The production of the peptides can be carried out either synthetically by imitation of the molecule or by biological means by inducing its manufacture by bacteria. The venture capital companies have not been mistaken: 4 million euros will not be too much, but the game is worth the candle.

Pesticides, warming: agriculture has found "its limits"

Whether to reduce pesticides or to combat the effects of global warming on plants, agronomic research "progresses" and "gives rise to a lot of hope", explains to AFP the President of INRA , Philippe Mauguin.

"The general approach of the National Institute of Agricultural Research", presented this week at the Agriculture Fair, "focuses on the diversity of resources within a single species" to explain how "crosses of wild varieties naturally resistant to certain diseases can genetically reinforce varieties currently used in agriculture or arboriculture," said Mauguin in an interview on Wednesday.

Because according to him, l French agriculture as it has existed since the Second World War "has found its limits".

After the war, "we had organized the choices of varietal selections with the aim of feeding the country, and we have multiplied yields by three in a few decades thanks to genetic selections, inputs and agrochemistry. "

" But we saw the limits of this system in the late 1990s, with case of water pollution, especially via the effects induced by a weed-killer, atrazine, which was finally banned in 2003 but which leaves long-lasting effects ", underlines Mr. Mauguin.

For several years, Agriculture has tried to correct the side effects of chemistry on the earth and the environment, with "reasoned" practices that limit the use of pesticides.

"But the answers were not fast enough, and we saw the limits of the plan + Ecophyto +", launched by President Sarkozy in the wake of the Grenelle Environment Forum, admits the one who was director of cabinet from the previous Minister of Agriculture Stéphane Le Foll: "a simple optimization of the use of phytosanitary products is not enough".

– Radical Change –

After stating that "farmers do not use pesticides for pleasure, but to protect their crops, "Mr. Mauguin stresses that the goal is to" change the entire agricultural production system in a radical way. "

" But it is not obvious ", recognizes -he.

He presented Tuesday the new agronomic approaches under study to Ministers Frédérique Roussel (research) and Nicolas Hulot (Ecological Transition).

The first is the increase of biocontrol, that is to say Neutralization of aggressors with their predators, usually insects. Trichogramma, for example, destroys corn borer, which attacks maize in particular

The second approach is to improve varietal selection in order to make seed varieties more resistant to diseases and thus limit the use of chemical pesticides.

INRA presents on its stand the first four vine stocks from its research, carrying genes resistant to powdery mildew and mildew, which will reduce by more than 70% the use of pesticides on the market. vine: Vidoc, Voltis, Floreal and Artaban

"In January, we included in the catalog of varieties these first four resistant grape varieties, two for red wines and two for white wines," says Mauguin. INRA is expected to release about twenty more in 2019.

This approach is developed for all species. "We accompany the seed companies for the first stage of propagation" and then they continue, explains Mr. Mauguin.

On some species the work is very long and frustrating. For lettuce, for example, "in 20 years, we have found about 30 resistant genes, but the aggressors still bypass, defend themselves and we must constantly seek new resistant genes."

On the disputed herbicide glyphosate, INRA estimates that it is able to offer alternatives "that can be complicated to set up" for 80% to 90% of use cases.

"We evaluated technical dead ends between 10% and 20%", essentially in the field of soil conservation agriculture, says Mauguin.

This type of agriculture is of great interest in the fight against global warming, since by removing plowing, it can store carbon in the soil. But it requires the use of a weed killer once a year to clean the soil before sowing, to allow the seeds to grow.

Agricultural Show: Biocontrol Solutions to Exit Pesticides

NATURAL. Pheromones, bacteria, macroorganisms, vegetable, animal and mineral substances. In recent years, the battery of natural solutions acting on plant health has grown steadily. "The 43 French companies members of our International Association of Manufacturers of Biocontrol Products (IBMA) have a turnover of 2 billion euros, or 5% of the national pesticide market ]details Fabrice Favrot, CEO of Koppert France, a subsidiary of a Dutch company specializing in the sector. We are aiming for 15% by 2020. "

The winds are indeed very buoyant. After years of failed plant protection product reduction policies that are now found in most French rivers, governments and a growing share of the agricultural profession seem to really want to solve the problem. Koppert sums up the vitality of the sector. This company, created in 1967, started with greenhouse crops, a specialty of Holland. In a controlled and closed world, it is indeed easier to use natural weapons that are four in number:

Macro-organisms are the class of natural predators of insect pests of plants. This is the case of the ladybug on aphids, trichograms against corn borer, typholodromes against mites of the vine. 100 000 of the 500 000 hectares of maize planted in France are treated by trichogrammes

The micro-organisms are the bacteria and viruses effective as well against the insects as against the mushrooms. The bacterium Pythium oligandrum acts against Fusarium wilt, Beauvaria bassiana against corn borer, Bacillus thurigiensis against Colorado potato beetle

] Pheromones are odorous compounds that allow male insects to meet females. By diffusing these "perfumes", one institutes a "sexual confusion" which hinders the reproduction. This technique is now common in arboriculture and viticulture.

Vegetable, animal and mineral substances are extracts having an effect on plants. This is the case of paraffin oils, sweet orange essential oils, and pyrethrins extracted from chrysanthemum.

These techniques target plant pests. There are also products for stimulating plant defenses. Thus, "elicitors" are compounds extracted from algae that strengthen the immune defenses of plants. Another method of improving the robustness of crops is the provision of plant-friendly bacteria and soil fungi. Research has shown that soil micro-organisms matched to improve plant resistance to pests. These communities are reconstituted and sprayed on crops. The main company of the sector, Novozymes, joined in 2013 the multinational Monsanto to develop this solution. "Research is particularly dynamic in our sector, welcomes Fabrice Favrot. Thus, we will go from 3 to 10 treatment solutions for diseases of cereals and from 1 to 7 for other field crops, maize, rapeseed, in the coming years. "

Accelerate research efforts [19659009] This progress is particularly expected by farmers who fear being left without solutions to diseases. This is in any case the position of the FNSEA which refuses any ban on chemicals if there is no alternative treatment. However, biocontrol is only part of the solution to reduce or even eliminate the chemistry of farms. Agronomic solutions such as rotations with introduction of legumes, reduction of plot sizes, use of computer alert systems complete the arsenal of measures to be implemented. All these solutions are studied within a public-private consortium that is now being asked to accelerate research efforts.