5. APIMIR
ARENABUNYAL
Year Start: 2011
Call for projects:
ANR (ANR2010 - BLANC)
Global budget: 600 k€
Public funding: 600 k€
Duration: 48 months
Stage of development at the beginning
of the project: Basic research
Accredited by: Lyonbiopole
PARTNERS
Partners
Laboratory Adaptation and
Pathogenicity of Microorganisms UMR 5163 (Research unit)
Institut Pasteur (Research unit)
Large Scale Biology (BGE) - U 1038
(Research unit)
Public funders
NR, Agence Nationale de la
A
Recherche
ongoing projects
Abstract
This proposal focuses on the basis of
host cell manipulation by Plasmodium
and Toxoplasma, the agents of malaria and toxoplasmosis, respectively.
MicroRNAs are a class of small noncoding RNAs that modulate the gene
function at the post-transcriptional
level and act as a fine tuner of various
biological processes, such as development or immunity. Inspired by the work
on viruses and bacteria, we recently
started to explore whether Plasmodium
and Toxoplasma co-opt, impinge on, or
subvert microRNA-directed functions as
a means to alter gene expression in host
human cells.
Strategic business area
Project leader
HAKIMI Mohamed-Ali
Entity: CNRS
Position: Research Professor
Address: UMR5163, Domaine de la Merci
38700 GRENOBLE
Email:
Mohamed-ali.hakimi@ujf-grenoble.fr
Phone: +33 (0)6 77 43 79 54
Objectives
To examin the human small microRNome patterns following T. gondii and P. berghei
infection.
To select pertinent microRNAs and experimental validation of their target (genes)
pathways.
• For those that have all the attributes, we will investigate more deeply how they contri
bute in host cell to promote or prevent parasite infection by using microRNA depletion
and overexpression.
• To identify parasite effector molecules (small RNAs or proteins) that hijack the RNA
silencing machinery in the host cell.
Innovative assets
Structural, mechanistic and inhibitor design studies of the Bunya - and
Arenavirus L-proteins
Year Start: 2011
Call for projects:
ANR (ANR2011 - BLANC)
Global budget: 2 204 k€
Public funding: 350 k€
Duration: 36 months
Stage of development at the beginning
of the project: Basic research
Accredited by: Lyonbiopole
Abstract
The ARENABUNYA-L project aims to
derive a structure-based, mechanistic
model to explain how arena- and bunyavirus RNA polymerases function in both
transcription and replication of the viral
genome. Transcription in these viruses
is performed by ‘cap-snatching’ but
this occurs in the cytoplasm, whereas
influenza virus does this in the nucleus.
Structural information on cap-snatching
will be used to optimise inhibitors as a
first step towards antiviral drug design.
Strategic business area
The microRNA matured in multiple steps in the cells is taken
into the RNA-induced silencing complex (RISC) to regulate
mRNA expression and stability.
Recent data point to the possibility that
apicomplexans alter the host
microRNome, thereby identifying the
RNA silencing pathway as a new means
by which they reshape their cellular
environment. We identified a large
number of host genetic riboregulators
whose expression was tightly regulated
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LYONBIOPOLE
by Toxoplasma infection. We also report
that two immunomodulatory microRNAs
contribute to better control of parasite
burden in the brain and promoted resistance to Toxoplasma infection.
Scientific publications
2
Partners
aboratoire Architecture et Fonction
L
des Macromolécules Biologiques
(AFMB) (Research unit)
uropean Molecular Biology
E
Laboratory (EMBL) (Research unit)
Public funders
NR, Agence Nationale de la
A
Recherche
Project leader
CUSACK Stephen
Entity: European Molecular Biology
Laboratory
Position: Head of Outstation
Address: 6, rue Jules Horowitz
38042 Grenoble
Email: cusack@embl.fr
Phone: +33 (0)4 76 20 72 38
Objectives
The overall goal of this project is to derive a structure-based, mechanistic model to
explain how segmented, negative-strand RNA viral polymerases function in both transcription and replication.
Innovative assets
We will use recombinant arena- and bunyavirus RNA polymerases and complexes with
viral RNA to study in vitro polymerase mechanisms by biochemical and structural biology methods.
Application fields
Infectious diseases
Technological approaches / Keywords
Structural Biology
Toxoplasma and Plasmodium subversion of
host cell miRNAs for parasite intracellular
development
Application fields
Infectious diseases
Technological approaches / Keywords
Genetics / Genomics
Actual Outcomes
PARTNERS
Schematic diagram of the architecture of cap-snatching, segmented negative strand RNA viral polymerases. The polymerases of
different genera are represented as lines with the size in amino acid residues of the representative species shown. The blue box
at the left indicates the endonuclease domain with the particular sequence signature of that genus written above. The central box
represents the conserved polymerase domain. In the case of orthomyxoviruses (e.g. influenza), the three subunits PA, PB1 and PB2
of the heterotrimeric polymerase are represented co-linearly with the total number of residues shown. The blue box in influenza PB2
represents the cap-binding domain, which is possibly located in the C-terminal region of the other L-proteins (question mark).
Perspectives
Set-up of a new RD project
Clinical trial realization
Actual Outcomes
We have determined the crystal structure of the nucleoprotein of La Crosse
orthobunyavirus in complex with single-
stranded RNA and proposed a model of
how it packages the RNA genome.
Scientific publication
1
LYONBIOPOLE
9
ongoing projects
Toxoplasma and Plasmodium subversion of host cell miRNAs for
parasite intracellular development
6. BBMUT
NEW
Artificial testis for fertility preservation of children with cancer
Year Start: 2013
Call for projects: Proof of concept CLARA
Global budget: 1 250 k€
Public funding: 355 k€
Duration: 36 months
Stage of development at the beginning
of the project: Preclinical development
ongoing projects
Abstract
While sperm cryopreservation before
starting oncological treatment is efficient
for fertility preservation in adult males,
in prepubertal children only spermatogonia are available from testicular
tissue, and no system of maturation are
currenty available. The company Kallistem and academic partners (Université
Claude Bernard Lyon 1, Hospices Civils
de Lyon, INSERM, CNRS, INRA) developped a prototype of «artificial testis» to
perform ex vivo spermatogenesis from
immature testicular tissue. The financial
support of CLARA will be determinant
to transfer this method from rat to
humans.
PARTNERS
Partners
Hospices Civils de Lyon (Healthcare
unit)
Kallistem (Company)
Inserm U846 (SBRI) (Research unit)
UMR CNRS 5223 (IMP) (Research unit)
Public funders
onseil général de Rhône
C
rand Lyon
G
Project leader
LEJEUNE Hervé
Entity: Centre Hospitalier Universitaire
de Lyon
Position: Professor of Endocrinology
Address: Hôpital Femme Mère Enfant
59, bd Pinel - 69500 Lyon
Email: herve.lejeune@chu-lyon.fr
Phone: +33 (0)4 72 12 97 92
Objectives
One child out of 500 is affected by cancer. More than 75% of them will be cured. Hence,
1/1000 young adult (20-30 y.o.) is a cancer survivor. These therapies are known for their
gametotoxic effects that can cause sterility. The aim of the ARTIS project is to develop a
system to produce mature sperm cells ex-vivo, from germline stem cells contained in
immature testicular tissue. This includes preclinical studies in the rat for safety issues.
The final objective is to preserve fertility of prepubertal boys before oncological treatment known to induce sterility by spermatogenic failure.
Innovative assets
Strategic business area
Application fields
Oncology
Technological approaches / Keywords
Cell model / Animal model / Cell therapy
/ Regenerative Medicine
The whole ARTIS project is innovative. To our knowledge no “artificial testis” are currently available. The main steps of the project are:
• Production of sperm cells in sufficient amount to perform ICSI,
• Study the quality of ex-vivo produced sperm cells in rat,
• tudy the quality of conceptus in the rat (anatomo-physiological and comportmental
S
studies),
• Transfer to human testicular tissues and study the quality of ex-vivo produced human
sperms and finally,
• Determine the practical and ethical conditions for a clinical trial in prepubertal boys.
Actual Outcomes
Perspectives
In vitro spermatogenesis was studied in
our group from 1997 (Weiss et al. Biol Reprod. 1997;57:68-76). In 1999 we published
that one application of in vitro spermatogenesis will be to preserve fertility in prepubertal boys before oncological treatment
(Lejeune H, Durand P. Conservation de
tissu testiculaire et maturation in vitro de
la lignée germinale pour préservation du
potentiel de reproduction avant traitement
anticancéreux chez le garçon pré-pubère.
Andrologie, 1999;9:498-504.) The system
is now advanced enough to propose the
development of this project for a clinical
application.
Clinical trial realization
Proof of concept
Patents
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LYONBIOPOLE
testimony
Pr. Hervé Lejeune, clinician pratician at
Hôpital Femme Mère Enfant
The genesis of the project goes back to
the publication in 1999 of joint results with
Philippe Durand on the conservation of
testicular tissue and the in vitro maturation
of the germ line. The idea of ARTIS took
place during the 2010 Industrial-Academic
Meetings of CLARA, when Laurent David’s
team presented its work on the application
of biopolymers in cell culture. Experiments
are conducted and the project becomes
credible when the last steps of the in vitro
spermatogenesis are conducted. The par-
Broad Band ultrasound imaging using CMUT
Year Start: 2012
Call for projects:
ANR (ANR2011 - TECSAN)
Global budget: 2 032 k€
Public funding: 782 k€
Duration: 42 months
Stage of development at the beginning
of the project: Basic research
Accredited by: Lyonbiopole
Abstract
The early diagnosis of liver diseases
and/or identification of any focal lesions
are key issues to consider a favorable
prognosis. These objectives require
non-invasive dedicated diagnostic tools
and justify the development of innovative
techniques. The BBMUT project aims
to exploit the properties of a promising
new technology of ultrasound probes,
called CMUT, to propose new techniques
for imaging and characterization of liver
tissue. The CMUT probe, developped by
the company Vermon, is characterized
by a large frequency band. The harmonic
imaging techniques will be especially
investigated.
Strategic business area
Application fields
Oncology
Technological approaches / Keywords
Imaging (medical) / Ultrasound
PARTNERS
Partners
REATIS (Research unit)
C
ospices Civils de Lyon (Healthcare
H
unit)
ermon (Company)
V
MR930 «Imagerie et Cerveau»
U
(INSERM) (Research unit)
aboratoire de Mécanique et
L
d’Acoustique (LMA) - UPR 7051
(Research unit)
Public funders
NR, Agence Nationale de la
A
Recherche
Entity: CREATIS
Position: Professor
Address: 7, av. J. Capelle 69621 Villeurbanne
Email: olivier.basset@creatis.univ-lyon1.fr
Phone: +33 (0)4 72 43 85 69
Objectives
• esign of a CMUT probe whose specifications are adapted to the examination of the
D
liver Implementation of innovative techniques based on Chirp or composite signal
emission.
• upply of a native image that has improved contrast without degrading the resolution.
S
• evelopment of an ultrasonic method for characterizing tissue structures adapted to
D
liver.
• uantitative measurement of the nonlinearity parameter.
Q
• re-clinical validation to quantify the diagnostic relevance of the proposed approaches.
P
Innovative assets
The innovative aspects of the
project consists in the development of specific imaging
technique for image improvement or tissue characterisation
dedicated to the large bandwidth
of cmut probe.
Cmut probe and ultrasound image of a circulating contrast agent using a harmonic imaging technique
tnership with academic and clinical actors
materializes when the company Kallistem
is created in 2012.
To us, CLARA promotes the synergy
between partners involved in the project.
Through its selection in the CLARA Proof
of Concept program, and its financing by
territorial collectivities, the support of
ARTIS corresponds to one the 2009-2013
Cancer Plan which focuses on improving
access to the preservation of fertility in
cancer patients.
The specificity of the Proof of Concept
programs allows us to be accompanied by
CLARA on the regulatory aspects and in
our approach to Health authorities.
Project leader
BASSET Olivier
Actual outcomes
3 Scientific publications
4 Communications in international congresses
Perspectives
Preclinical assay realization
LYONBIOPOLE
11
ongoing projects
ARTIS
9. CHEMISPIKE
CLARENCE
Inhibition of syndecan-1 mediated cell adhesion
ongoing projects
Abstract
Syndecans are transmembrane heparan
sulfate proteoglycans widely expressed
in developing and adult tissues. Several
studies report involvement of syndecans
in human diseases such as cancers and
infectious diseases. Among these, a syndecan-1 interaction with laminin 332 was
shown to influence epithelial cell behavior and potentially impact carcinoma
development. Through a high-throughput screening assay of a large library of
chemical agents at the « Plateforme de
Criblage de Molécules Bio-Actives », we
have identified promising inhibitors of
the syndecan-1 mediated cell adhesion
pathway.
Strategic business area
Application fields
Infectious diseases / Oncology
Technological approaches / Keywords
Analytical Chemistry / Chemotherapy /
Functional Screening / Drug discovery /
Structural Biology
PARTNERS
Partners
Institut de Biologie et Chimie des
Protéines (IBCP) - UMR 5305 (CNRSUCBL1) (Research unit)
Conception, synthèse et vectorisation
de biomolécules - Institut Curie /
CNRS UMR 176 (Research unit)
IBS - INSTITUT DE BIOLOGIE
STRUCTURALE - UMR 5075 (Research
unit)
Public funders
ANR, Agence Nationale de la
Recherche
Project leader
ROUSSELLE Patricia
Entity: Laboratoire de Biologie Tissulaire
et Ingénierie Thérapeutique - Institut de
Biologie et Chimie des Protéines - UMR
5305 CNRS UCBL
Position: Research Director
Address: 7, passage du vercors
69367 Lyon
Email: patricia.rousselle@ibcp.fr
Phone: +33 (0)4 72 72 26 39
Objectives
The proposal CHEMISPIKE aims at:
• Dissecting the molecular mechanism underlying the syndecan-1 mediated cell adhe
sion cascade,
• Identifying, among the hits coming from the screening, specific syndecan-1 inhibitors
and determine their intracellular target,
• Characterizing/optimizing the selected molecules through medicinal chemistry and
test their potential anti-tumoral properties in vitro using colon and breast carcinoma
cells
• Solving the structure of the laminin 332 domain involved in syndecan-1 interaction
using X-ray crystallography.
Year Start: 2012
Call for projects:
ANR (ANR2011 - P2N)
Global budget: 10 k€
Public funding: 520 k€
Duration: 36 months
Stage of development at the beginning
of the project: Basic research
Accredited by: Lyonbiopole
Abstract
As exposure to environmental carcinogens may increase the risk of sporadic breast cancers, it is important to
decipher the role of environmental
carcinogens in the chronic carcinogenesis of human breast epithelia and their
contribution in the development of this
cancer. The CLARENCE project aims to
use a tumor progression model of breast
cancer that mimics progression from the
benign to the premalignant status and
from the premalignant to the malignant
status to study the impact of chronic and
low-dose exposure to two environmental
carcinogens.
Strategic business area
Innovative assets
The major innovative asset of Chemispike relies on the fact that syndecan-1 inhibitory
molecules were tested in the context of a cell adhesion assay. Molecules were selected
upon their potential to inhibit syndecan-1
mediated adhesion to laminin and were
shown to operate at the intracellular level
most likely targeting the syndecan-1 signaling cascade. In addition to its impact in
oncology, this project could have an impact
in the treatment of infectious diseases as
syndecan-1 is known to be an important
receptor/co-receptor involved in some
The chemispike project aims at identifying and developing
bacterial and viral pathogens, mediating
small molecules with potential to inhibit the interaction of the
infection.
cell adhesion receptor syndecan-1 expressed at the surface of
Application fields
Health Environment / Oncology
Technological approaches / Keywords
Biobank / Cell model / Animal model /
Minimally Invasive Technologies
epithelial cells with proteins of the microenvironment.
Actual Outcomes
The major innovative asset of Chemispike relies on the fact that syndecan-1
inhibitory molecules were tested in the
context of a cell adhesion assay. Molecules were selected upon their potential
to inhibit syndecan-1 mediated adhesion
to laminin and were shown to operate at
the intracellular level most likely targeting the syndecan-1 signaling cascade.
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LYONBIOPOLE
In addition to its impact in oncology,
this project could have an impact in
the treatment of infectious diseases as
syndecan-1 is known to be an important
receptor/co-receptor involved in some
bacterial and viral pathogens, mediating
infection.
Scientific publications
8
8 ommunications in international
1 C
congresses
2 PhD
Perspectives
PARTNERS
Partners
épartement Cancer et
D
Environnement, Centre Léon Bérard
(Research unit)
RCL, Inserm U1052-CNRS 5286
C
(Research unit)
’Institut de Recherche en
L
Cancérologie de Montpellier (IRCM U896) (Research unit)
aboratoire HydroSciences
L
Montpellier (UMR5569 CNRS,IRD,
UM1, UM2) (Research unit)
lateforme de Recherche en
P
Toxicologie Environnementale et
Ecotoxicologie (Research unit) Voir le
sitePROFILEXPERT (Company)
Public funders
NR, Agence Nationale de la
A
Recherche
Project leader
COHEN Pascale
Entity: Département Cancer et Environnement, Centre Léon Berard
Position: Professor
Address: 28, rue Laënnec 69373 Lyon
Email: pascale.cohen@univ-lyon1.fr
Phone: +33 (0)4 78 77 28 94
Objectives
• o identify and establish an original in vivo or in vitro biological model that could allow
T
the study of candidate environmental molecules
• o investigate the cellular, molecular, epigenetic, transcriptomic and metabolomic
T
impacts of chronic and low-dose [B(a)P and/or BPA] exposure in a tumor progression
model of breast cancer
• o perform in vivo investigation
T
• o identify putative human candidate biomarkers of BPA and/or B(a)P exposure and
T
putative molecular targets that could be used by agents to overcome environmental
exposure
Innovative assets
The overall novelty of the research program is the strategy focused on the combination
of two environmental molecules possessing two different mechanisms of toxicity and
tested in a model of
tumor progression in
breast cancer. This
is in contrast with
classical approaches
aimed at testing
each environmental
molecule individually,
thus overlooking the
potential cross-talk
and potentialization
between different
environmental
molecules.
Characterization -Optimization Establishment of exposed cell mini-bank
Preclinical assay realization
Search for private financing
Search for public funding
Actual outcomes
Perspectives
2 Communications in international
congresses
Scientific publications
LYONBIOPOLE
17
ongoing projects
Year Start: 2009
Call for projects: ANR (ANR2008 - PCV)
Global budget: 2 020 k€
Public funding: 625 k€
Duration: 56 months
Stage of development at the beginning
of the project: Basic research, Discovery,
Accredited by: Lyonbiopole
Cellular, molecular and genomic investigation of chronic environmental exposure
of low doses pollutants in a tumour progression model of breast cancer
11. DDELPHES
An innovative automated system for online detection of microorganisms in water
Year Start: 2011
Call for projects: FUI (FUI AAP11)
Global budget: 3 271 k€
Public funding: 1 149 k€
Duration: 36 months
Stage of development at the beginning
of the project: Basic research
Accredited by: Lyonbiopole
Co-accredited by: Axelera, Risques
Partners
Bertin Technologies (Company)
Cylergie, Centre de recherche de
Cofely (Company)
CEA LETI (Research Unit)
Ademtech (Company)
Amoéba (Company)
Suez environnement (Company)
Public funders
Fonds Unique Interministériel (FUI) –
DGCIS/Oséo
Grand Lyon
FEDER PACA
Project leader
TROUCHET Daniel
Entity: Bertin Technologies
Position: Senior Expert
Address: 10, bis Avenue Ampère
78180 Montigny-le-Bretonneux
Email: trouchet@bertin.fr
Phone: +33 (0)1 39 30 60 34
ongoing projects
Abstract
Objectives
Three decrees respectively in 2004 and
2010, impose a follow-up of Legionella
in wet cooling towers and sanitary water
network. The classic strategy which
consists in increase organic and inorganic substance amounts cannot be an
answer to the microbiological treatment.
Then, DDELPHES proposes to develop a
full automated system, enabling analysis
of the micro-organisms present in water
(bacteria and amoeba). This system will
make possible to carry out an uninterrupted follow-up of the microbiological
quality of water and, by consequence,
better control the treatment application.
The objectives are the development of standalone subsystems for Sampling and
concentration of the water, DNA preparation and automated qPCR on a chip, and then
the development of a standalone integrated device (demonstrator) allowing rapid and insitu analysis of micro- organisms in water systems. The Microbial targets are Legionella
spp and pneumophila, Amoebae (Naegleria fowleri, Willaertia). The device will allow for
automated water sampling, on-line analysis and results sending within a few hours. It
will be tested on field with a view to industrialization and marketing of a product.
Localized delivery of chemotherapy induced by ultrasound
Year Start: 2013
Call for projects: Proof of concept
CLARA
Global budget: 1 061 k€
Public funding: 435 k€
Duration: 24 months
Stage of development at the beginning
of the project: Preclinical development
The DDELPHES project aims to develop a standalone, in situ and fast analysis system
based on qPCR. Up to now, such devices do not exist. The project will be based on a
combination of advanced technologies involving biology, automation and miniaturization
in order to obtain a compact, sensitive and robust equipment. Amoeba real time
monitoring could allow for “green treatment” using them as biological agents.
Partners
SERM U1032 (LabTAU) (Research
IN
unit)
aviskills (Company)
C
entre Léon Bérard (Healthcare unit)
C
Public funders
onseil général de Rhône
C
rand Lyon
G
Abstract
Acoustic cavitation can be defined as the
dynamic of bubbles of vapor under an
ultrasonic field. It is clearly established
in the literature that cavitation favors
transmembrane penetration of molecules and increases the ratio efficacy /
toxicity of chemotherapies. The project
would allow testing on preclinical models a therapeutic prototype combined
with conventional drugs and performing
clinical pilot study on selected targets.
Strategic business area
Innovative assets
PARTNERS
Application fields
Oncology (Breast, Sarcoma)
Technological approaches / Keywords
Chemotherapy / Ultrasound
Project leader
LAFON Cyril
Entity: INSERM U1032 (LabTAU)
Position: Senior investigator - Team
leader
Address: 151, cours Albert Thomas
69424 Lyon CEDEX 03
Email: cyril.lafon@inserm.fr
Phone: +33 (0)4 72 68 19 20
Objectives
The present project aims at developing an ultrasonic medical device that could
potentialize chemotherapy for the treatment of various cancers. Negative hormone
receptors breast cancer (207 000 cases/year) and soft-tissue sarcoma (4000 cases/year)
have been identified as potential targets. Both cancers do not respond well to available
treatments. The conventional chemotherapies demonstrated their relative efficacy but
remain associated to a significant systemic toxicity. The non specific distribution of the
cytotoxic drugs results in reduced therapeutic efficacy and side effects.
Innovative assets
INSERM filed a patent on a method for stabilizing ultrasonic cavitation. The company
CAVISKILLS SAS licensed this patent and aims at exploiting this idea by developing a
clinical device for delivering chemotherapeutic drugs locally. The goal is to enhance the
efficacy the treatment and reduce associated side effects. The treatment is completely
non invasive and performed under ultrasound imaging guidance.
Strategic business area
Health Environment
Application fields
Health Environment
Technological approaches / Keywords
Biochips
Functional decomposition DDELPHES tasks
Actual Outcomes
Up to now a standalone concentration
device, a sample preparation module
and a qPCR module have been developed at the prototype stage. Uptake
and extraction protocols and kits have
been developed and tested. The limits of
detection obtained are better than required for amoeba. For legionella, they are
good when bacteria are in clean water
but not with cooling tower water, which
is an important issue to solve.
Product, prototype, service
1
1 concentration module 1 sample prep
module+ 1 qPCR module
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LYONBIOPOLE
Sustainable Job creations at the
2
end of the project
Perspectives
Product marketing
Automated concentration module
TESTIMONY
Daniel TROUCHET, Bertin Technologies
“The DDELPHES project addresses
a major public health concern (water
microbial contamination) and the
consortium balance between research,
industry and end-users, ensures to
have at project disposal the available
key technologies necessary to reach its
goals, which were the key points for the
funding of the project. The partnership
has been built mainly through networking and it was already partially set via
former projects collaborations when
Bertin joined it. Lyonbiopôle participated
in the consortium final elaboration, and
in particular they helped to find a key
partner (Ademtech) and to define the
work program. They also contributed
to keep the development with a view of
industrialization and marketing of a product and facilitated scientific exchanges
between experts during the project
progress.”
Schematic of the Caviskills clinical device for treating soft tissues sarcomas
Actual outcomes
TESTIMONY
Products, prototypes, services
Clinical trials
Press release
Cyril Lafon, senior researcher at LabTAU
INSERM Unit
For the past few years, LabTAU laboratory
has worked in close relationship with
the CLB (Léon Bérard Cancer Center),
particularly on the clinical application of
ultrasounds, and with the CRCL (Cancer
Research Center of Lyon) on the transfection theme. In 2011, CLARA allowed
its collaborations to catalyze by putting in
contact the founders of Caviskills.
When CLARA financed CLUB, an emerging
Perspectives
Set-up of a new RD project
Clinical trial realization
Product marketing
Search for private financing
Search for public funding
project, partners were able to carry out a
preliminary market study, thus allowing us
to validate the interest for the technology
and to select clinical targets. The interest
of the collaboration proposed via the CLARA Proof of Concept program is to be able
to bring together complementary regional
actors essential to the implementation of
such a pluridisciplinary project (academics
for engineering sciences and biology with
clinicians and industrials).
LYONBIOPOLE
21
ongoing projects
PARTNERS
DELICHIUS
NEW
14. ETICS
NEW
Accelerated development program of immunotherapy solutions against emerging
diseases
Year Start: 2012
Call for projects: ISI Oséo
Global budget: 26 620 k€
Public funding: 9 507 k€
Duration: 63 months
Stage of development at the beginning
of the project: Discovery
Accredited by: Lyonbiopole
ongoing projects
Abstract
The EMER-IT program proposes to build
a complete value chain for developing,
producing and commercializing innovative specific polyclonal immunoglobulins
against at least four emerging pathogens
(such as Encephalitis of Nipah, Ebola
hemorrhagic fever or Lassa, SARS).
These specific polyclonal immunoglobulins will be produced with an ambitious
immunization approach that will be
implemented by using synthetic nanovectorization of antigens in DNA form.
The proof of concept of efficacy of each
specific polyclonal immunoglobulin
product will then be established.
PARTNERS
Partners
AB’ENTECH (Company)
F
n-Cell-Art (Company)
I
IRI - equipe Enveloppes virales et
C
ingéniere des rétrovirus (Research
team)
Laboratoire Jean Mérieux P4 - Inserm
(Research unit)
Institut du thorax (Inserm U915)
(Research unit)
Public funders
Oséo / BPI France
Project leader
VACHER Laurent
Entity: Fab’entech
Position: RD programs leader
Address: Immeuble Domilyon,
321, Avenue Jean Jaures - 69007 Lyon
Email: laurent.vacher@fabentech.com
Phone: +33 (0)4 37 70 67 67
Objectives
• Identify and select the appropriate strains of highly pathogenic viruses according to
epidemic needs and health risks
• Develop, manufacture and commercialize specific polyclonal immunoglobulins against
emerging infectious diseases
• Develop an innovative antigen approach using synthetic DNA nano-vectorization of VLP
to be used for horse hyperimmunization against any emerging pathogens targeted
• Implement a pilot plant for the GMP production of specific polyclonal immunoglobulin
products
• Develop a new DNA-based veterinary vaccine for horses by In-Cell-Art
Innovative assets
Strategic business area
Application fields
Infectious disease
Technological approaches / Keywords
Immunotherapy
• DNA-based antigen nano-vectorization
• Virus-Like Particles (VLP) nano-vectorization
• Innovative platform for the develoment and flexible production of specific polyclonal
immunoglobulins
• Single-use based pilot plant for GMP production of immunoglobulins
Evolved Tissue Inspired Cell Systems
Year Start: 2011
Call for projects: ISI Oséo
Global budget: 14 400 k€
Public funding: 7 600 k€
Duration: 60 months
Stage of development at the beginning
of the project: Preclinical development
Accredited by: Lyonbiopole
PARTNERS
Partners
YTOO Cell Architects (Company)
C
ellectis (Company)
C
EA iRTSV France (Research unit)
C
Public funders
séo / BPI France
O
Entity: CYTOO SA
Position: CEO
Address: MINATEC -BHT-B52 - 7 Parvis
Louis Néel - BP50 - 38040 Grenoble
Email: mlebozec@cytoo.com
Phone: +33 (0)4 38 88 47 05
Abstract
The use of more relevant cells during
pharma-tox screening would help the
search for new drugs and pick up toxicity
issues earlier. Conversion however to 3D
cell culture represents a huge challenge
as it is badly adapted to the constraints
of automated screening and high content
imaging and analysis. The ETICS program aims at providing an alternative
option: combine the potential of adhesive
micropatterns, soft substrates and standardized fluorescent cell lines enabling
more physiological cellular models
and reliable high content imaging and
analysis optimized for pharma-tox drug
screening.
Project leader
LEBOZEC Marc
Objectives
The ETICS program aims to provide cell models that are more physiologically relevant
as well as better suited for high content imaging and analysis (HCA) than conventional
methods. This will be obtained by cultivating cells on micropatterned surfaces with
softness properties similar to the original tissue. Specific fluorescent cells lines
expressing standardized levels of fluorescent proteins will be used to demonstrate
that more meaningful and reproducible experimental results are obtained under these
conditions.
Strategic business area
Application fields
All pathologies area
Technological approaches / Keywords
Cell model / Genetics / Genomics
A model illustrating the combination of soft surfaces, adhesive micropatterns and fluorescent cells
Human epidemics recorded for 6 emerging diseases
Actual Outcomes
Products, prototypes, services
Clinical trials
Product on the market
Job creation in Rhône-Alpes region
26
LYONBIOPOLE
Perspectives
Search of competences
Product marketing
LYONBIOPOLE
27
ongoing projects
EMER-IT
15. FEMTOKINE
FLUMA
Year Start: 2010
Call for projects: FUI (FUI AAP10)
Global budget: 2 170 k€
Public funding: 1 267 k€
Duration: 48 months
Stage of development at the beginning
of the project: Clinical trials
Accredited by: Lyonbiopole
Co-accredited by: Eurobiomed
ongoing projects
Abstract
PARTNERS
Partners
DICIA BIOTECHNOLOGY (Company)
IN
ospices Civils de Lyon (Healthcare
H
unit)
xCell (Company)
T
INGULEX (Company)
S
Public funders
FEDER Rhône-Alpes
Fonds Unique Interministériel (FUI) –
DGCIS/Oséo
Grand Lyon
Région Rhône-Alpes
Project leader
LEGASTELOIS Stéphane
Entity: Indicia Biotechnology
Position: CEO
Address: 33, avenue de la Californie
69600 Oullins
Email: slegastelois@indicia.fr
Phone: +33 (0)4 72 39 14 92
Different conformations of the Influenza virus matrix protein M1 and their role
during entry and budding
Year Start: 2011
Call for projects:
ANR (ANR2010 - BLANC)
Global budget: 314 k€
Public funding: 212 k€
Duration: 36 months
Stage of development at the beginning
of the project: Basic research
Accredited by: Lyonbiopole
• Biobanking: patients in clinical remission induced by surgical or drug therapeutic
management and patients under cellular therapy
• Immunoassay validation following FDA guidelines
• New immuno-assay development
• Kit’s adaptation for intestinal biopsy diagnostic
• Samples analysis to validate immunological biomarkers as predictors of clinical
recurrence of CD:
- T cell analysis in blood and in biopsies
- Determination of immunological markers in plasma and biopsies
- Measurement of inflammation markers in serum and stools
Influenza viruses contain three major
subviral components: the envelope, matrix protein 1 (M1) and the core harboring the RNA genome. M1 forms a shell
beneath the viral envelope that sustains
the virion architecture. Upon acidification of the virion within the endosomes,
M1 undergoes a conformational change
resulting in disassembly of the M1 matrix, virus uncoating and the release of
the vRNP into the host cell. The project
aims to elucidate the structural basis of
M1 activation of Influenza virus assembly and budding and establish the exact
roles of M1 during these processes.
Strategic business area
Innovative assets
Strategic business area
Application fields
Autoimmune diseases
Technological approaches / Keywords
Biobank / Immunomonitoring
• High sensitive immunoassays
for the prediction of relapses of
Crohn’s disease and therapeutic
follow –up.
• Clinical validation of biomarkers
Technical development
and clinical validation of
immunoassays.
Application fields
Infectious diseases
Technological approaches / Keywords
Structural Biology
The accuracy of immunologic biomarkers to predict the relapse of CD
might be superior to that of inflammatory markers and requires ultrasensitive methods for immunomonitoring immune responses.
Actual Outcomes
testominy
1 Product, prototype, service
Communication in international
1
congress
License Agreement
1
Sustainable Job creations at the
2
end of the project
1 Job creation in Rhône-Alpes region
1 Start-up Creation
Creation of Singulex Europe subsidiary
in 2010
Increase in turnover
Stéphane LEGASTELOIS, Indicia
“Singulex and Indicia signed a partnering
agreement by which Indicia acquired the
rights to use the new Singulex’s Erenna
Immunoassay platform. The technology
is dedicated to the measurement of
cytokines and other biomarkers at the
femtogramme level. This level of performance makes possible the monitoring
of immunological disorders in human
inflammatory diseases such as Crohn
disease
28
LYONBIOPOLE
Femtokine was built around partners
having access to human patients suffering from Crohn disease. Hospices Civils
de Lyon and TxCell were both conducting
clinical trials on this pathology. Singulex
RD Europe provides the technology
while Indicia offers the Immunoassay
plateform and sample analysis.
Lyonbiopole gave significant support to
identify partners, prepare the project
submission file and give assistance in
the follow-up of the project”
Partners
nit of Virus Host Cell Interactions U
UMI 3265 (Research unit)
Public funders
NR, Agence Nationale de la
A
Recherche
Project leader
WEISSENHORN Winfried
Entity: Unit of Viral Host Cell Interaction
(UVHCI)
Position: Professor, team leader
Address: 6, rue Jules Horowitz, BP181
F-38042 Cedex 9 Grenoble
Email: weissen@embl.fr
Phone: +33 (0)4 76 20 72 81
Abstract
Femtokine aims to develop tools dedicated to the identification and validation
of immunological biomarkers that are
specifically involved in Crohn Disease
(CD), a chronic inflammatory pathology
of the digestive tract. The disease suffers
from a lack of non invasive biomarkers
that are needed to assess the severity of
the pathology, together with the efficacy
and toxicity of therapeutic treatments.
The project consists of generating a bank
of samples from CD patients, measuring
and validating a panel of biomarkers
based on an unique and ultra-sensitive
proteomic plate-form.
Objectives
PARTNERS
Objectives
• stablish the cloning, expression and purification of full-length M1 protein derived from
E
different Influenza strains.
• creen for crystallization conditions for full-length M1 protein at neutral and low pH. To
S
facilitate crystallization of M1 in different conformations we will generate conformation
specific llama VHH nanobodies and try co-crystallization with known complex partners.
• Determination of high resolution structures of full-length M1protein.
• stablish conditions that allow us to study protein coat formation by M1 in vitro.
E
Innovative assets
The project concentrates on the structural biology of the complete viral matrix protein
M1. We hypothesize that the crystal structure of a complete M1 protein will provide
important insight into its
function during uncoating
and during assembly and
budding. Our work might
provide novel insight into
the ESCRT-independent
budding of influenza virus
and the structural details
of M1 at neutral and low pH
will help to develop anti-viral
agents that target entry or
assembly.
Schematic model of an influenza virion. The matrix protein M1 has an elongated
shape in solution (inset M1 model based on SAXS data) and forms a protein layer
underneath the viral membrane. During entry this protein coat must dissassemble to
allow establishment of a new infection.
Actual Outcomes
•W
e have shown by NMR that the matrix
protein M1 undergoes conformational
changes at endosmal pH, which may
be important for uncoating.
• e have solved the crystal structure of
W
M1 from influenza C, which resembles
globally the structure of M1 from
influenza virus A.
• e have assemble low resolution
W
models of influenza virus A and C
based on SAXS data.
• e have analyzed the membrane binW
ding properties of influenza virus A and
C M1 proteins
Perspectives
Search for public funding
Part of the project is funded by the Labex
GRAL
1 Manuscript in preparation
LYONBIOPOLE
29
ongoing projects
High sensitive immunoassays for the prediction of relapses of Crohn’s disease and therapeutic follow
–up. Clinical validation of biomarkers Technical development and clinical validation of immunoassays