PDP2022-10
Quantitive micromethods for rapid characterization of immune cells activity in infection and cancerous context
Host laboratory and collaborators
Olivier Theodoly / INSERM / olivier.theodoly@inserm.fr
Pascal Rihet / TAGC / pascal.rihet@univ-amu.fr
Abstract
The diagnosis of immune defaults and the design of immune therapies suffer from a lack of quantitative tools to characterize the multiple and complex steps of immune responses. In particular, fast monitoring of immune cell activation would permit rapid assessment of infectious, autoimmune, or cancerous risks. We recently validated a prototypic method to analyze phenotypically and at single cell level the activation of leukocytes from a drop of patient blood. The method, currently considered for a patent, is based on multiprotein micropatterning with micron size resolution. The generated smart substrates have multiple specific functions towards lymphocytes, such as selection, capture, activation and read-out. Rapidity and automatization of the method, together with access to the kinetics of activation at single cell level are key assets to shed new light on physiopathologic questions and to offer new diagnosis opportunities for acute pathologies. We propose here to develop and apply such innovative tools to the cases of sepsis, malaria and immunotherapy treatments.
Keywords
sepsis, immunotherapies, immune, cells activation, microfluidics, protein printing
Objectives
The prototypes for immune cell activation assays are currently under valorization. With the biophysical team (Supervisor 1), they will be tested for different immune cells. With the biological and medical team (supervisor 2), they will be applied to perform fast prognosis of patients at risk of sepsis or malaria, as well as to stratify the patients response to immunotherapies in order to identify the 2/3 of patients who could benefit from earlier indication at the first relapse, or even as a first line treatment.
Expected profile
The candidate should have experience in biology and/or biophysics, and a marked interested in microtechnolgies and medical trandfer.
Is this project the continuation of an existing project or an entirely new one?
New one.
2 to 5 references related to the project
Luo, X.; Noray, V. S. de; Aoun, L.; Biarnes-Pelicot, M.; Strale, P.-O.; Studer, V.; Valignat, M.-P.; Theodoly, O. Lymphocytes Perform Reverse Adhesive Haptotaxis Mediated by LFA-1 Integrins. J. Cell Sci. 2020, 133 (16). https://doi.org/10.1242/jcs.242883
Rosier F, Nuñez NF, Torres M, Loriod B, Rihet P*, Pradel LC*. Transcriptional Response in a Sepsis Mouse Model Reflects Transcriptional Response in Sepsis Patients. Int J Mol Sci. 2022 Jan 13;23(2):821. doi: 10.3390/ijms23020821.
Thiam A, Sanka M, Ndiaye Diallo R, Torres M, Mbengue B, Nunez NF, Thiam F, Diop G, Victorero G, Nguyen C, Dieye A, Rihet P. Gene expression profiling in blood from cerebral malaria patients and mild malaria patients living in Senegal. BMC Med Genomics. 2019 Oct 30;12(1):148. doi: 10.1186/s12920-019-0599-z.
Venton G, Labiad Y, Colle J, Fino A, Afridi S, Torres M, Monteuil S, Loriod B, Fernandez-Nunez N, Farnault L, Suchon P, Mattei JC, Rihet P, Bergon A, Nguyen C, Baier C, Costello R. Natural killer cells in acute myeloid leukemia patients: from phenotype to transcriptomic analysis. Immunol Res. 2016 Dec;64(5-6):1225-1236. doi: 10.1007/s12026-016-8848-0.
3 main publications from each PI over the last 5 years
Olivier Theodoly
Aoun, L.; Nègre, P.; Gonsales, C.; Seveau de Noray, V.; Brustlein, S.; Biarnes-Pelicot, M.; Valignat, M.-P.; Theodoly, O. Leukocyte Transmigration and Longitudinal Forward-Thrusting Force in a Microfluidic Transwell Device. Biophys. J. 2021, S0006349521002927. https://doi.org/10.1016/j.bpj.2021.03.037
Aoun, L.; Farutin, A.; Garcia-Seyda, N.; Nègre, P.; Rizvi, M. S.; Tlili, S.; Song, S.; Luo, X.; Biarnes-Pelicot, M.; Galland, R.; Sibarita, J.-B.; Michelot, A.; Hivroz, C.; Rafai, S.; Valignat, M.-P.; Misbah, C.; Theodoly, O. Amoeboid Swimming Is Propelled by Molecular Paddling in Lymphocytes. Biophys. J. 2020, 119 (6), 1157–1177. https://doi.org/10.1016/j.bpj.2020.07.033.
Valignat, M.-P.; Nègre, P.; Cadra, S.; Lellouch, A. C.; Gallet, F.; Hénon, S.; Theodoly, O. Lymphocytes Can Self-Steer Passively with Wind Vane Uropods. Nat. Commun. 2014, 5, 5213. https://doi.org/10.1038/ncomms6213
Pascal Rihet
Rosier F, Brisebarre A, Dupuis C, Baaklini S, Puthier D, Brun C, Pradel LC*, Rihet P*, Payen D*. Genetic Predisposition to the Mortality in Septic Shock Patients: From GWAS to the Identification of a Regulatory Variant Modulating the Activity of a CISH Enhancer. Int J Mol Sci. 2021 May 29;22(11):5852. doi: 10.3390/ijms22115852. *co-corresponding authors
González A, Artufel M, Rihet P. Nucleic Acids Res. TAGOOS: genome-wide supervised learning of non-coding loci associated to complex phenotypes. 2019 Aug 22;47(14):e79. doi: 10.1093/nar/gkz320.
Baaklini S, Afridi S, Nguyen TN, Koukouikila-Koussounda F, Ndounga M, Imbert J, Torres M, Pradel L, Ntoumi F, Rihet P. Beyond genome-wide scan: Association of a cis-regulatory NCR3 variant with mild malaria in a population living in the Republic of Congo. PLoS One. 2017 Nov 9;12(11):e0187818. doi: 10.1371/journal.pone.0187818. eCollection 2017. PMID: 29121672