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UMR_S 1036 CEA/Inserm/Université de Grenoble

Cancer Biology and Infection laboratory

Published on 4 June 2015

The Biology of Cancer and Infection laboratory (1036 UMR_S CEA / Inserm / UJF) was created by the association of several research teams from iRTSV, who wished to address some major challenges of cellular and molecular biology related to human health. These research interests concern mainly bacterial infections and cancer. Our methodological approaches range from biochemical study of protein systems (either isolated or in macromolecular complex) to pathophysiological studies using overexpression or invalidation of genes of interest in animal models (mainly murine).

The main objectives of the BCI lab are both to increase our understanding of the mechanisms of infection and cancer at the molecular level and to develop applications of medical interest in terms of diagnosis and treatment. The remarkable technological potential of iRTSV (high throughput screening of chemical and siRNA libraries, quantitative proteomics, performant microscopy) will be a key competitive asset in achieving our goals.
In more detail, our activities are based around the following questions:

• Infection
The emergence of antibiotic-multiresistant bacterial strains has become a public health problem. Many Gram-negative bacteria responsible for serious infections such as pneumonia, diarrhea or fever, are affected by this phenomenon. One of the strategies to combat this health problem is to study the molecular mechanisms of virulence in order to identify new therapeutic targets and stimulate the discovery of new drugs. BCI is interested in the molecular mechanisms of bacterial pathogenesis and in the cell responses to infection. We study the secretion systems involved in the export of toxins at the functional and structural level, especially in the pathogenic bacteria Pseudomonas aeruginosa.

Endothelial cell (nucleus stained in blue) during infection by Pseudomonas aeruginosa (bacteria stained in green).

Signaling pathways as well as toxins targets are studied in different cell models by considering both the pathogen and the target eukaryotic cell. In this context, collaboration with the team BGE / BioMics was initiated to screen the human kinome by siRNA approach during host-pathogen interaction. We participate in the DSV research program on biosafety by studying anti-infection therapeutic targets and candidate vaccines against major pathogens. Molecular tools from our work will be applied to the characterization of hyper-virulent clinical strains (collaboration with the University Hospital of Grenoble) and to the screening of chemical libraries for new antibiotics. This implies our long-standing collaboration with IBS to develop a comprehensive knowledge of the target structure at the atomic level.

• Cancer
Recent advances in anti-cancer therapies came from targeted therapies. Despite progress, much remains to be done in identifying relevant molecular targets and developing inhibitors of these targets with minimal side effects. BCI has chosen to focus on two types of targets: protein kinases deregulated in cancer cells and tumor blood vessels whose growth is a prerequisite for the growth and metastasis of cancerous tumors. Our approach is twofold: to understand the mechanisms and develop diagnostic tools and/or therapeutics.

The blood (red) and lymphatic (green) vascular networks in mouse tail dermis. The endothelial cells lining these vessels are the study subjects of the BCI laboratory.
Confocal microscope at our institute, x20 magnification

In collaboration with the University Hospital of Grenoble and the BGE/BioMics team, siRNA screening of all kinases from the human genome will be undertaken on miniature models of three-dimensional cultures of human renal tumor cells to determine the combination of essential kinases required for the growth of these tumors.
Mechanisms of angiogenesis are being studied in the physiological environment such as the development of the placenta during pregnancy and the pathological context, especially during tumor angiogenesis. We focus our studies on the EG-VEGF growth factor and its PROKR receptors, the endothelial receptor ALK1 and its ligands BMP9 and 10 and VE-cadherin, a constitutive protein of inter-endothelial adherens junctions. Serum determinations of EG-VEGF, BMP9 and soluble forms of VE-cadherin and ALK1 are the subject of several clinical studies in which their interest is evaluated as diagnostic biomarkers.
Furthermore, a new multi-target therapeutic strategy involving the biological properties of the RNA-binding protein Tis11b was recently validated in a murine model of cancerous tumors. An orthotopic model adrenocortical tumor progression developed in our laboratory will be used to refine the new anti-tumor treatment.

BCI is a founding member of two Federative Research Structures in the University Grenoble-Alpes: iRTSV and GIRC (Grenoble Institute for Research on Cancer). Its ambition is to continue to advance excellence in research, interaction with scientific partners from CEA Grenoble-G and UJF and, more broadly, with its French and international collaborators.


Université Grenoble Alpes submits its application to the IDEX Project

The ambition shared by the partners of the project – the universities Joseph Fourier, Pierre Mendès France and Stendhal; the grandes écoles Grenoble INP, Sciences Po Grenoble and ENSAG; the national research organisms CNRS, CEA, Inserm, Inria, Irstea; and the university hospital CHU Grenoble – is focused on creating a single world-class university: the future new University Grenoble Alpes. This new model of university will reinforce our capacity to attract leading scholars and students, develop ground-breaking research and competitive curricula. UGA will be a fully integrated institution. [more]

Université Grenoble Alpes : "1 out of 5" 

One person out of five living in Grenoble works in research, innovation or higher education…
The BCI laboratory supports the IDEX.

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