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  • 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.

    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.

    Contact and documentation

    Contacts de la recherche à l'UTC

    Contact

    Direc­teur du labo­ra­toire GEC
    Kars­ten Haupt
     +33 (0)3 44 23 44 55

    Pla­quette de la recherche à l'UTC

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