Description of the thesis topic

This thesis is about the development of an electrochemical hybrid peptide-carbon nanotube biosensors for the detection of Protein Kinases (PK) activities involved in the joint inflammation of juvenile idiopathic arthritis (JIA) and Septic arthritis (SA). The goal is to 1) profile functional PK signatures and 2) design a diagnostic device allowing rapid and accurate discrimination between both diseases. The peptides conjugated onto CNTs and PKs will be provided by the project partners in Strasbourg and Montpellier. At Grenoble, these conjugates will be evaluated determining the most appropriate transduction technique for electrochemical quantification of PK activities. This hybrid biosensor will be implemented to profile PK activities in the synovial fluid of juvenile arthritides in a highly sensitive and selective fashion. This technology should contribute to improve screening campaigns by enabling identification of disease biomarkers and patient stratification at an early-stage, guiding clinicians in their choice of PK-targeted therapies. This interdisciplinary research project requires a high level of interest and curiosity in fundamental research. Developed communication skills and the ability to organise and design experiments independently are essential for the efficient accomplishment of this project.

Work Context

Septic arthritis (SA) and juvenile idiopathic arthritis (JIA) are the most frequent forms of arthritis in children, caused by bacterial infection and autoimmunity, respectively. Their different etiology requires opposite treatments: surgical drainage and antibiotics for SA, anti-inflammatory and/or immunosuppressive therapy for JIA. However, no sufficiently sensitive diagnostic markers enable differentiation between these conditions upon initial presentation. Protein Kinases (PKs) involved in regulation of inflammation and immune response are dysregulated in several inflammatory pathologies, constituting attractive pharmacological targets for therapeutic purposes, as exemplified by targeting of Janus family of kinases by Tofacitinib in JIA. Although an arsenal of Food and Drug Administration (FDA)-approved PK inhibitors is available for clinical therapies, there are currently no diagnostic approaches based on detection and quantification of PK activities.
This thesis is funded by the project ANR KINFLAM in collaboration with Alberto Bianco in Strasbourg, who will provide the functionalized carbon nanotubes, and May Morris in Montpellier, who will produce the kinases and specific peptides. The experiments will be done primarily at the DCM in Grenoble, with several planned visits to the partners. The DCM is a joint unit of the University of Grenoble Alpes and the CNRS, with approximately 80 permanent researchers and teaching researchers, and is composed of six research teams working in the fields of organic, inorganic, analytical, theoretical chemistry, and electrochemistry. The thesis will be carried out in the BioSEN team (Bioelectrochemistry for Sensors, Energy, and Nanomaterials; 9 permanent staff), which has extensive expertise in the development of electrochemical biosensors.
The supervisors ensure that the PhD student has a high-quality working environment and the financial, material, and human resources necessary for the research. The thesis director and co-director also provide the PhD student with the benefit of their professional network, helping them to participate in scientific events and bringing them in contact with other researchers in this research field.
It should be noted that the position is located in a sector covered by the protection of scientific and technical potential (PPST), and therefore requires, in accordance with regulations, that your arrival will be authorized by the competent authority of the Ministry of Higher Education and Research (MESR).

The position is located in a sector under the protection of scientific and technical potential (PPST), and therefore requires, in accordance with the regulations, that your arrival is authorized by the competent authority of the MESR.

Constraints and risks

No particular constraints and risks. All chemical use and modification procedures will be trained during supervision respecting safety and security regulations.