Image
Image
Image
Image
Image
Image
Image
Introduction team

The multidisciplinary research team SyNaBi has taken a bioinspired approach to develop innovative biotechnologies for medical applications.

Scientific theme and general objectives

Nature is full of complex things that are elegant in their methods of fabrication. Inspiration from such elegant natural processes provides a path to develop new biotechnology systems to produce power and to create new medical diagnostic and therapeutic devices. The path is complex, but successful biomimicry of biological processes usually results in highly sensitive biotechnology devices. From its understanding of protein-lipid interactions, the SyNaBi team has pioneered the biotechnology for the production of power using biological membrane transport proteins incorporated in a biomimetic lipid bilayer membrane. The biomimetic lipid bilayer is an important bioinspired core component, which is self-assembled using principles derived from natural biology.

The research field of SyNaBi is based on combined skills of the team in

  • Bioengineering of biomimetic membranes and biocompatible polymers, 
  • Biophysic and modeling,
  • Molecular and cellular biology, 
  • Bioelectrochemistry, electrophysiology and biochemistry.
Research topics

Implantable biofuel cells and biosensors:

We chose two biomimetic approaches to create bioinspired biofuel cells. The first was an enzymatic biofuel cell that generated electrical current from redox mechanisms. The second was a biomimetic biofuel cell that generated an electrical potential from ion transfer across a biomimetic membrane. The enzymatic biofuel cell, utilizing glucose and oxygen, is theorically able to work almost indefinitely as its substrates are always present in the body fluids. However, the biocompatibility and the long-term performance of this biofuel cell for a human implantation remains a real bottleneck. We are working on the design and the implantation of new enzymatic biofuel cells in different animal models. The implantation of such devices is challenging and a novel creative solution is to take a physiological point of view to address biocompatibility problems and electrical measurement techniques. We are now capable to implant these biofuel cells in large animals by analyzing the performance of the biofuel cells in real time.
We also initiate the biomimetic biofuel cell concept. It consists of a membrane transport protein (i.e ion channels) incorporated in a biomimetic membrane, which transforms a gradient of salt into a proton gradient. We also generate a 20 mV voltage with a 38 mm² flat membrane. This biomimetic membrane containing the NhaA sodium/ proton exchanger is stable for more than two weeks.

The use of immobilized enzymes or biomimetic membranes incorporating transport proteins allows us to create and open out a huge range of biosensors. The ceration of the biosensors also benefits from the miniaturization we are able to achieve through the application of nanotechnology, such as by the principles described here.
 

Other implantable devices:

We also focus on innovative medical devices capable of modifying the gut microbiota,involved in many pathologies (e.g morbid obesity, diabetes, chronic inflammatory diseases, Parkinson's disease). We are optimizing an intestinal reactor able to consume nutrients, modify the physicochemical conditions to which the microbiota is sensitive and produce molecules of interest. This reactor and a microbiota sampler are yet tested in vivo. Those two projects are supported by the  SATT Linksium (Technology transfert & startup building).
 

Systems for personalised medicine and HTS :

We develop these systems by relying on the concepts of “biomimetics”. This concept was first introduced by Otto Schmidt in 1969 during a presentation at the 3rd International Biophysics Congress in Boston. Such a biomimetic approach, also used in the field of nanobiotechnologies, means that the fabrication processes for the systems are based on the way that natural systems a “self-assembled”. An example is our involvement in the UroLOC project, which is an ambitious scheme in collaboration with scientists from the CEA and CNRS to develop a nanostructured 3D polyelectrolyte scaffold that is connected to a microfluidic biochip to examine the influence of the microenvironment on cancerous cells from the prostate and to identify new biomarkers for prostate cancer.

This basic research has already given rise to 2 patents and 3 publications, one in the journal Biomaterials, where we show that a positively-charged polyelectrolyte film of only several nanometres in thickness reduced the clustering and proliferation of cancerous prostate cells.

Our ongoing work is developing those fundamental results into a diagnostic device for personalized medicine and high-throughput-screening (HTS).

Research Programs
Research Programs

Actual grants

  • ANR - projet BIOWATTS
  • ANR - projet IMABIC
  • SATT - projet BIOPILE
  • SATT - projet MICROBIOTE SAMPLER
  • SATT - projet MODULATEUR MICROBIOTE
  • Ligue Contre le Cancer - projet VE-Cadherin  / phospholipids
  • ValoGRAL - projet UroLOC

Grants 2011-2016

  • Investissement d’Avenir - projet IBFC 
  • ANR - projet BROCOLI
  • ANR - projet M-GBFC
  • Horizon 2020 - projet UroLOC (complementary list)
  • AGIR-UGA - projet MEKANO

Subvention LIGUE

Supervisor(s): Donald MARTIN
Contract: LA LIGUE CONTRE LA CANCER Isère - CNRS - [2017-2018]
Nanobiotechnology utilized in the search for better understanding of interactions between cancer biomarkers et lipoproteins.

Projet pré-maturation start-up BIOPILE

Power from the body for the body
Supervisor(s): Philippe CINQUIN
Contract: SATT Linksium, Technology transfer and startup building Grenoble Alpes - UNIVERSITE GRENOBLE ALPES - [2015-2017]
We have designed an enzymatic biofuel cell that uses glucose from the body to produce power for implantable devices. The biofuel cell is original in its method of production and its use of bioinspired solutions to overcome biocompatibility hurdles.
Project Page

ARC RÉGION

Supervisor(s): Don MARTIN
Contract: Région Auvergne-Rhône-Alpes, ARC 2016 ANNEE 1 - UNIVERSITE GRENOBLE ALPES - [2017-2018]
Biocathode manufacture and optimization.

Projet MICROBIOTA

Supervisor(s): Donald MARTIN
Contract: SATT Linksium, Technology transfer and startup building Grenoble Alpes - UNIVERSITE GRENOBLE ALPES - [2017-2018]

LIGUE

Supervisor(s): Donald MARTIN
Contract: LA LIGUE CONTRE LA CANCER Isère - CNRS - [2017-2018]

Projet IMABIC

Supervisor(s): Abdelkader ZEBDA
Contract: AGENCE NATIONALE DE LA RECHERCHE (ANR-16-CE19-0007) - UNIVERSITE GRENOBLE ALPES - [2016-2021]
Implantable Abiotic Biofuel Cell.
Project Page

Projet bioWATTS

Supervisor(s): Donald MARTIN
Contract: AGENCE NATIONALE DE LA RECHERCHE (ANR-15-CE05-0003) - UNIVERSITE GRENOBLE ALPES - [2015-2019]
Biomimetic membranes that produce biologically-inspired energy.
Project Page

Projet BIOPILE

Supervisor(s): Philippe CINQUIN
Contract: SATT Linksium, Technology transfer and startup building Grenoble Alpes - UNIVERSITE GRENOBLE ALPES - [2015-2017]

Projet TAENIA artificiel

Supervisor(s): Philippe CINQUIN
Contract: Convention de reversement CNRS - UNIVERSITE GRENOBLE ALPES - [2015-2017]
Team members

Team coordinator(s)

Permanent members

Others members

PhD students

Anciens membres de l'equipe

  • Barry Stidder (Postdoc)
  • Lavinia Liguori (Postdoc)
  • Landry Gayet (Postdoc)
  • Sarra El Ichi (Postdoc)
  • Geraldine Penven (PhD)
  • Thomas Soranzo (Postdoc)
Thesis

Synabi PhD thesis :

  • Béatrice BARLETTI : "Caractérisation nanostructurale des interactions protéiques avec les membranes bicouches lipidiques : base pour le développement de biocapteurs " (framed by Marco MACCARINI )
  • Thomas LECOURT : "Optimization of gold nanostructures electrodeposition for implantable enzymatic glucose biofuel cells " (framed by Abdelkader ZEBDA , MARC ZELSMANN (LTM UMR5129) )
  • Alexandre TRONEL : "Formulation de conservateurs du liquide intestinal du grêle à des fins d'analyses méta-omiques; implémentation sous forme anhydre dans des dispositifs de prélèvement non-invasifs ingérables " (framed by Donald MARTIN , Audrey LE GOUELLEC , Thomas SORANZO (Pelican Health) )
Platforms - Resources
Plateforme de Microscopie IntraVitale
Intravitale


La microscopie intravitale est outil qui permet d'analyser le fonctionnement des cellules saines ou malades dans un environnement complexe du vivant, avec la (patho)physiologie et la biologie tissulaire, cellulaire et moléculaire intacte. Pour obtenir ces informations complexes, un savoir faire unique a été développé sur la PF depuis 2002.

Notre mission est de réaliser des protocoles concernant la technique de microscopie optique, le traitement et l'analyse des images, permettant de comprendre comment les changements cellulaires, tissulaires et vasculaires évoluent dans le cadre d'un diagnostic et le suivi d'un traitement.

 


  Équipements :

  Informations plateforme

  • (à venir)

 

Responsable scientifique :

BvdSanden  Boudewijn van der Sanden

 boudewijn.vandersanden [at] univ-grenoble-alpes.fr
 06 48 54 67 12
 

 Intravitale

La plateforme (PF) a été labellisée par GiS-IBiSA en 2007 et France Life Imaging en 2012.

 

Primary collaborations and grants

National collaborations

  • In Grenoble :
    • CEA (iSTRV/BGE, LETI, INAC)
    • ILL (Institut Laue Langevin)
    • LGP2
    • LRB
  • in France :
    • Université de Clermont Ferrand
    • ICBMS Lyon
    • Creancey
    • Paris HEGP
  

International collaborations

University of East Anglia, Norwich Medical School (U.K.). MESA+ Institute for Nanotechnology. University of Twente (The Netherlands). Tyndall National Institute (Ireland), University of Turku (Finland). University of Melbourne (Australia)

Industrial collaborations

  • France : Synthelis SAS, Sorin Group, Biopic SAS. ST Microelectronics, Groupe Absiskey - Vitamib, 
  • International : Creamedix GmbH (Allemagne), Mosaiques Diagnostics GmbH (Allemagne),0stendum R&D b.v. (Pays-BAS), Seagull Technologies Pty Ltd (Australie), SDX Tethered Membrancs Pty Ltd (Australie)
Teaching-Training

Jean-Pierre Alcaraz

  • is teaching in BIO4111  for Master1 in Biology "experimental approch in biology".

Donald Martin

  • responsible of UE MCMB7U00 "Outils Moléculaires en Santé" de M1 Ingénierie pour la Santé /Science et Management des Biotechnologies (SMB)
  • responsible of UE MCXA0008 UE "Micro and Nanotechnologies for Health" de Master 2 ISM
  • is teaching in UE ‟Biosensors and high throughput analysisˮ - 5PMBBTA7 Grenoble INP Phelma

Philippe Cinquin

  • Mathematic in PACES (Grenoble)
  • Biostatistics in PACES (Grenoble)
  • GMCAO  Master Informatique Bio Médicale (Paris)

Contact

don.martin-at-univ-grenoble-alpes.fr
Phone: 00 33 456 52 00 95
Address: Faculté de Médecine de Grenoble, Pavillon Taillefer, 38706 La Tronche