BIOC is affiliated with CNRS Biology and Ecole Polytechnique. As part of its development, BIOC increasingly integrates processes from the atomic to the supra-molecular and cellular levels, in order to understand and engineer biological phenomena of fundamental and technological interest. It addresses questions related to fundamental cellular processes (protein synthesis, cell migration, cell signaling), to evolution as well as to pathologies (cancer, neurodevelopmental disorders and neurodegenerative diseases). BIOC research is strongly interfaced with other disciplines and with teaching at IP Paris. 

BIOC is organized in six teams. BIOC uses and develops techniques and methods from biochemistry, molecular biology, cell biology, structural analysis, cryo-electron microscopy, and computational biology. Questions related to biotechnology and synthetic biology have become more prominent, including efforts towards genetic code expansion. Biomedical questions have increased even more, with the arrival of two teams addressing possible precision medicine for cancer and neurodegenerative diseases. This is in line with growing societal challenges and with the IP Paris "Engineering for Health" initiative. The research topics of each of the teams are described briefly below.

GENERAL THEMES

The "Biocomputing and Structure" team (PI: T. Simonson) develop and apply computational methods for studying and engineering biomolecular interactions. Approaches include molecular dynamics (MD) and in-house tools for computational protein design (CPD). The team develops theories, methods and software, and uses the available tools to address biological and engineering issues, such as expansion of the genetic code. 

The main activity of the "Translation Mechanisms" team (PIs: E. Schmitt and Y. Mechulam) is to identify molecular specificities of the ribosomal translation machinery in the three domains of life, using a variety of structural and biochemical methods. The team invested substantial efforts in developing tools to determine the structures of ribosomal complexes using cryo-electron microscopy at Ecole Polytechnique. A large part of the studies focuses on Archaea models. Archaea, known for their diverse habitats ranging from extreme environments to common biotopes like soil and the human microbiota, exhibit fundamental informational mechanisms closely resembling those of eukaryotes, particularly in protein biosynthesis. The arrival of an INSERM researcher demonstrates a commitment to understanding human health issues at the molecular level, in line with the strategies of CNRS, Ecole Polytechnique and IP Paris. 

The "Translation and degradation of eukaryotic mRNAs" team (PI:M. Graille) uses biochemical, structural and cell biology approaches to understand the role of eukaryotic RNA post-transcriptional modifications. Most RNA components participating in mRNA maturation and translation undergo many small and diverse post-transcriptional chemical modifications, which enhance the efficiency, fidelity and regulation of fundamental biological processes such as mRNA maturation, stability or translation. Once deposited, these modifications can be recognized by specific proteins (readers) that influence RNA fates. These modifications are largely evolutionary conserved but their roles have long been neglected due to the frequent lack of obvious phenotypes or the unknown nature of the enzymes (writers) adding these marks. The team aims to decipher their role in central biological processes, in cell proliferation, in organ development and to describe the consequences of pathogenic mutants. 

The “RNA and Ribosome Homeostasis” team (PI: S. Ferreira-Cerca) was initiated in 2023 with the arrival of S. Ferreira-Cerca as a CNRS senior scientist, with starting funding from CNRS and EP. This team aims to better understand the principles of RNA and ribosome homeostasis, leading to an improved conceptual framework regarding the evolution of RNA metabolism, and to provide information about functional convergence and divergence within the different domains of life. Moreover, the “RNA and Ribosome Homeostasis” team aims to exploit its expertise to develop archaea-based biosynthetic gene regulation circuits and/or engineered bioreactor systems and, more generally harness its accumulated knowledge to develop possible applications.

The “Cytoskeleton in cell morphogenesis” team (PI: A. Gautreau) strives to understand the role of the actin cytoskeleton in the remodeling of cell membranes. Numerous multiprotein complexes are involved, such as the Arp2/3 molecular machine which creates branched actin networks that generate a pushing force. The team mainly addresses the regulation of Arp2/3 in normal cells and its deregulation in cancer. The team is looking for new Arp2/3 regulators, then combining cell biology with biochemistry to decipher how the molecular machines at play in actin polymerization assemble after subunit translation, and how they function in force generation and mechanosensing. Finally, the team is addressing the basic mechanisms of cell transformation during cancer progression using the sequential introduction of driver mutations into the genome of normal cells. This allows the team to examine how molecular machines are deregulated by the stepwise transformation of cells, but also to gain a detailed understanding of the synergy of driver mutations found in patient tumors in terms of phenotypical changes and drug sensitivity. 

BIOC has just recruited the team “Signal Transduction and Therapeutic Targets in Neurodegenerative Diseases” (PI: B. Schneider). The team tackles basic and clinical challenges relating to neurodegeneration/neurotoxicity in prion and Alzheimer’s diseases and, more recently, Amyotrophic Lateral Sclerosis (ALS). The team provided prime evidence for the implication of common neurodegenerative mechanisms converging to plasma membrane cellular prion protein (PrPC) and the corruption of PrPC signaling function by diverse unrelated amyloid proteins. The team also uncovered that PrPC relays the toxicity of some nanoparticles (titanium dioxide-TiO2, Carbon black-CB) of our environment through the same signaling pathways as amyloids. The effectors (e.g., the kinases ROCK, PDK1, PDK4) deregulated downstream of PrPC are potential therapeutic targets on which it is possible to act pharmacologically to counteract the neurotoxicity of amyloids or nanoparticles and limit the progression of the neurodegenerative diseases.

Disciplines - Methodologies

• Molecular and structural biology (X-crystallography and cryoEM)
• Biochemistry of proteins and nucleic acids
• Physical biochemistry
• Bioinformatics 
• Cell Biology

TEACHING

Organization and supervision of biology practical courses of the Biology Department of the Ecole polytechnique (6000 hours.students/year)
Master mention "Biology and Health" at IP Paris
68 theses from 1975 to 2020