The first part of Le Novère's career, in the laboratory of Jean-Pierre Changeux at the Pasteur Institute, was focused on studying Nicotinic acetylcholine receptors in the brain.

[5][6] During his post-doctoral fellowship in the group of Dennis Bray at the University of Cambridge, he modeled the molecular networks underlying bacterial chemotaxis.

[7][8] Le Novère then became involved in the development standards to share mathematical models such as SBML,[9] of which he would later become editor.

The group studied the signaling pathways underlying synaptic plasticity, in particular the allosteric calcium sensors.

[10][11][12] In parallel, his group coordinated the development of a consistent set of standards in systems biology, including the graphical notation SBGN,[13] the guidelines MIRIAM[14] and MIASE,[15] the languages SED-ML[16] and PharmML, and ontologies[17] such as the Systems Biology Ontology.