We are looking for a PhD candidate with a Master 2 in bioinformatics or related to defend our project in the doctoral school of Aix-Marseille Université: https://ecole-doctorale-62.univ-amu.fr.
This project is a collaboration between Marc Dalod at CIML (http://www.ciml.univ-mrs.fr) and Aitor Gonzalez at TAGC (https://tagc.univ-amu.fr). The laboratory of Marc Dalod focuses on the biology of immune cells using experimental and genomics approaches. The laboratory of Aitor Gonzalez focuses on integrative and bioinformatics methods. The successful student will be located in these laboratories based on the needs on the project. Both laboratories are located in the Campus of Luminy in Marseille closed to the beautiful Calanques.
The applicant must be interested in studying the immune system using integration of high-throughput transcriptomic and epigenomic data from single cell and bulk samples. Programming in R and Python is necessary. For applications, please send us the following documents by April 16th, 2023:
- Motivation letter
- Grades of the Master of Sc.
Contact email: email@example.com and firstname.lastname@example.org
PhD project description
Plasmacytoid dendritic cells (pDCs) are hematopoietic cells characterized by their unique ability to rapidly produce very large amounts of type I and III interferons in response to viral-type stimuli (Reizis, 2019). The identity of pDCs is ambiguous, as they possess a specific molecular identity card conserved between mouse and human, while sharing characteristics with both classical DCs (cDCs) on the one hand and lymphocytes on the other hand (Reizis, 2019). The balance between these three identity components varies according to the activation state of pDCs (Abbas et al., 2020). There is also controversy about the physiological functions of pDCs, including whether they play a beneficial role in the immune control of viral infections or a deleterious role in the development of certain autoimmune diseases.
Aims of this project
The global objective of the thesis project will be to perform bioinformatics analyses of genomic data to elucidate the ambiguous identity of pDCs and to infer hypotheses on their physiological role.
- Specific Aim 1: Determine the positioning of pDCs within an immune cell atlas.
- Specific Aim 2: Elucidate the molecular mechanisms of regulation of pDC identity.
- Specific Aim 3: Elucidate the molecular mechanisms of pDC activation from virus-like stimuli.
- Specific Aim 4: Analyze human genetic polymorphisms in the pDC genome and to look for a link with pathologies.
- Abbas, A., Vu Manh, T.P., et al. (2020). The activation trajectory of plasmacytoid dendritic cells in vivo during a viral infection. Nat Immunol 21, 983-997. 10.1038/s41590-020-0731-4.
- Ceribelli, M., Hou, Z.E., et al. (2016). A Druggable TCF4- and BRD4-Dependent Transcriptional Network Sustains Malignancy in Blastic Plasmacytoid Dendritic Cell Neoplasm. Cancer Cell 30, 764-778. 10.1016/j.ccell.2016.10.002.
- Reizis, B. (2019). Plasmacytoid Dendritic Cells: Development, Regulation, and Function. Immunity 50, 37-50. 10.1016/j.immuni.2018.12.027.
- Wimmers, F., Subedi, N., et al. (2018). Single-cell analysis reveals that stochasticity and paracrine signaling control interferon-alpha production by plasmacytoid dendritic cells. Nat Commun 9, 3317. 10.1038/s41467-018-05784-3.