Enzyme and Cell Engineering (GEC) – UMR CNRS 7025

The GEC Laboratory has a privileged position in French research acting as a federator for biological research in the Hauts de France region in associating UTC and Université de Picardie Jules Verne (Amiens). Positioned mid-way between biology and chemistry, GEC is a joint unit affiliated to the Institutes for Biological Sciences and Chemistry at the CNRS.

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Objectives

The research activities carried out at GEC are centered on the premise that solutions to scientific challenges are present in Nature. They combine three main approaches: utilization of bioresources, bioinspiration and biomimicry.

Building on its national and international acknowledged expertise in biotechnology, GEC implements various complex models to understand the biological processes and to find innovative solutions tailored to meet the scientific and societal needs and challenges.

Hence, the research activities of GEC are organized within exploitation of bioresources and plant metabolism, and development of bioinspired nanomaterials or molecular mimics dedicated to molecular recognition.

Research teams and thematics

The laboratory is currently gathering its research in two themes, while developing activities at the interface:

Theme Plant Metabolism and Bioresources

This theme tackles a set of scientific challenges related to lipid systems knowledge to modify metabolic pathways in order to improve plant oil yields, to produce unusual fatty acids and to better valorize bioresources by differential treatments of plant biomass, benefiting from its territorial anchoring. All of these activities take advantage of the whole plant to identify innovative sustainable processes, the results of which being usable in bio refinery. In this theme, other research topics arouse an increasing interest: the study of interactions between hosts (mainly plants) and pathogens (bacteria) by identifying mechanisms having roles in the initiation of bacterial colonization and insuring plant protection, as well as the study of the impact of climate changes on plant lipid metabolism.

Theme Biomimicry and Biomolecular Diversity

In this theme, two approaches complement each other, focused on biomimicry and bioinspiration. A first approach develops technologies aiming at obtaining artificial molecular diversity in which it is possible to select biomolecules of interest to specifically recognize identified targets. Molecular diversities can exceed billions, which is comparable to natural diversity of the immune system. A second approach develops functional nanomaterials dedicated to molecular recognition. With efficiencies comparable to those of antibodies, they can cover any scopes of application (health, food industry…) and may also fit to fundamental studies.

Academic partnerships

Institut national de la santé et de la recherche médicale (INSERM), Institut national de la recherche agronomique (INRA), Lund University (Suède), Queen Mary University (Londres, Royaume-Uni), université de Picardie Jules Verne (Amiens)…

Projcets

The GEC laboratory is developing projects in collaboration with other academic partners in France and abroad, in particular for ITE PIVERT.

Picardie Region projects

BIOMIP : Natural or synthetic origin bio-degradable materials play an increasingly important role in today's society, in packaging techniques, in agriculture and in medicine. The research teams are working on vectorisation systems that lead to new bio-degradable capable of interacting specifically with the targets and with modular or controllable activities.

In this project, the research team proposes development of bio-degradable (via enzyme activity) polymeric materials. The aim of the project is to design and develop new multi-functional materials for bothbio-medical and environmental purposes.

ITE PIVERT, EU programme GENESYS

ANOI is a programme to improve specific features of industrially attractive oil-bearing plants and to enable identification and classification of various possible oil-bearing plants and then to improve crop productivity for four model plants (colza 00, erucic acid colza, camoline and brassica carinata).

MetaLipPro-PL1 constitutes a knowledge acquirement phase that will enable the research teams to improve and complete our knowledge about lipoid metabolism for plants and for yeasts. Another aim is to establish the bases for the purpose of developing a pilot platform for lipid production and extraction.

The research work proposed will be developed in the framework of the VARIAPRO project 5 that will allow the scientist to establish the bases for pedoclimatic environmental varieties, and to follow the evolution of specific features selected in time, for the purpose of identifying efficient crop protection.

COPIBIOM, is a 3 year programme in cooperation with the UTC-TIMR lab, with UPJV (Jules Verne university) and the Glucid Valorisation Centre (CVG, Amiens),for the purpose of characterizing and studying new ligno-cellulose wet biomass pre-treatment protocols (colza and sunflower stems and leaves) and dry protocols (colza straw and outer shells, and sunflower shells).

Europena project

SAMOSS will lead to improvements of bio-sensors in a combination with opto-chemical detection techniques in various applications and via a large dissemination of the new knowledge obtained. SAMOSS will lead to the creation of a European 'excellence' centre for the training of young research scientists and development of bio-sensors adapted to applications in medicine, in agro-food and drink applications as well as for environmental questions.

ANR projects

The HOLOSENSE project aims at developing holographic bio-sensors using biomimic polymers with molecular prints (MIPs) as the recognition agents. MIPsare synthetic sensors that display affinities and selectivity levels comparable with those of antibodies or enzymes, but with a far higher degree of stability. They are obtained by polymerizing monomers in the presence of a "template" molecule (equivalent to a gauged dye-mould). This kind of economic and stable sensor, base as it is on using a MIP as thee recognition agent and on a hologram as the transducer has lots of potential for analyses in biomedical research, in the agro-food sector and in environmental work, in industrial sectors and even in day-today life.

The AcCatPat project focuses on the study of catalytic antibodies. The work includes analysis of physio-pathological relevance of catalytic antibodies for human patients, the identification of cat. V genes which encode the antibodies with catalytic activity and the development or relevant research tools specific to deciphering the molecular structures of catalytic antibodies and the ontogenesis and selection processes for the lymphocytes B that produce them.

The objectives assigned to the PT-flax project are to supply new genomic data about flax fibre and linseed and to build an important bio-resource, viz., aphenotype data base and the TILLing platform which will prove extremely useful for future genomic projects related to flax and its uses.

The Sorbonne universities cluster project

Microcystins (MC) are secondary metabolites produced by cyanobacteria, le latter being organisms that proliferate in ponds … MCs are toxic for all other aquatic life, for land-based animals and humans if their concentration in drinking water exceeds a certain threshold. This fact and observations has led the WHO (World Health Organization) to set contaminant threshold values. To comply with these values, various detection protocols must be implemented. Current approaches underscore the limits for immunotechnologies.

Consequently, the SelAcMC project aims at selecting antibody fragments that combat microcystins, and will lead to immune-detection tests to be used in various ecosystems. The main thrust of the project relies on using the Phage Display technique in order to identify one or several antibodies capable of specifically identifying one of the most common MC variants. The research team also envisage a parallel 'rationalization' approach using molecular modelling and biology specific computer sciences.

Zoom on 2 projects

Presenting UTC's mould wizards! And, at a molecular scale, Kartsen Haupt's research team at the Enzyme and Cellular Engineering (GEC) has a specialty number : producing polymers by molecular printing. "What we do is to mould rosin round a target molecule, for example, one that we wish to inhibit or block. The resulting shape print will then act as if it were an anti body, viz., a natural molecule that ensures the immune defence of our body and which in Nature fixes itself on the target to neutralise it."

Synthetic polymers obtained in this way can then replace antibodies and present certain other advantages : "the polymers are much more stable than the antibodies at ambient temperatures" stresses Kartsen Haupt. "And, sometimes it proves very difficult to produce the antibodies when the target molecules are too small". The GEC team have even been successful in producing reticulated polymers measuring only a few nanometres across: "we are down to nanoparticle level, i.e.,a level where they are soluble and therefore present new properties".

In 2004, a start-up was established, following the laboratory stages : Polyintell. This company provides the kits to meet bio-medical and agro-food demands. For example, these polymers can be used to reveal mycotoxins in food sample. The printed polymers are also very useful to separate two molecules that is close in structural composition. "In pharmaceutical applications, many drugs have two close formulae that we call enantiomers : one has the desired therapeutic property while the other may represent a potential danger for the patient." Using a very accurate print, the polymer used can separate the two forms.

A final point here. Karsten Haupt's team are studying currently possible uses of their polymers as a medicinal drug. "We mould the rosin on an enzyme. The polymer will become, for instance, an inhibitor drug acting like an antibody directed against this enzyme". The double advantage here is that the targeting can be far more accurate and many secondary undesired effects can be avoided.

Moreover, whereas injected antibodies can be rapidly degraded by other enzymes, polymers are less fragile and therefore remain in higher quantities and for a longer period in the patient's body. The next question is to learn how such polymers will be eliminated. "We are working on new rosins that would be formed by biodegradable vegetable molecules."

On one hand, we have the anti-bodies, which are the proteins produced by the million in response to an attack. "Any individual can produce upwards of a thousand billion different antibodies" says Alain Friboulet, director of the Enzyme and Cell Engineering Laboratory (UTC-GEC). The structure of antibodies is a beautiful Y‑shape.

On the other hand, we have the enzymes which are molecules but in far smaller quantities than the antibodies, and which have the capacity to accelerate chemical reactions within the cells themselves."Our objective was to have the antibodies acquire the biocatalytic specific to enzymes so that we can benefit from their extraordinary diversity."

But why, we may wonder, does UTC-GEC engage in this line of research? Enzymes are limited in number. And for certain jobs, e.g., cleaning of pesticide polluted soils, we just do not have the enzymes capable of destroying or degrading the molecules. Antibodies are specific to the immunity systems of mammals. If we given them new lines of possible action, by using enzymes, we are opening up the road to new treatments.

"We then imagined at UTC-GEC a truly biological method that proved successful." The biologists, in essence, advancing by successive enzyme prints, the whole system being produced by a mouse. "What we are doing is transfer the enzyme 'machinery' to the site where the antibodies would be fixed". Once the catalytic enzyme gene is recovered, we can reproduce it in large qualities, hence the advantage of a biological process.

The GEC team, as they progressed, saw that Mother Nature had in fact arrived first here. "For auto-immune illnesses such as multiple sclerosis, certain antibodies that attack the myelin of the nervous system are catalysed", notes Alain Friboulet. This discovery alone opened up numerous paths that could be used to protect people in certain illnesses, by identifying the relevant antibodies. Regularly, a certain number of kidney transplants are rejected two years after then operation, because of a necrosis of the vessels that surround the graft. "We detected in those patients where there was no graft reject, the presence of catalytic antibodies." There therefore exists a method to obtain a diagnosis based on the presence or not of catalytic antibodies and thus act upstream to prevent blood coagulation. In the case of multiple sclerosis, the UTC-GEC research scientists are collaborating with other teams in Russian research establishments. Studies on acquired haemophilia are also ongoing with an INSERM team resident at the Institut des Cordeliers.