DC 7 - Unveil the role of Land’s pathway as Treg immunometabolic checkpoint

• Objectives:

The objectives of the doctoral research program at the University of Milan are:

1. investigate the molecular pathway(s) linking Land’s pathway–dependent phospholipid remodeling with the Treg immuno-energetic phenotype,
2. dissect how LPCAT3 vs. PLA2, the enzymes involved in Land’s pathway, rewire cellular lipid composition and energetic metabolism to cope with Treg suppressive function,
3. target cellular phospholipid homeostasis by LPCAT3 vs. PLA2 inhibition to improve the Treg immunomodulatory response.

• Brief project description:

The overall aim of this doctoral research program is to identify the molecular circuits that link phospholipid metabolism to Treg suppressive function and test pharmacological approaches that, by targeting lipid pathways, would improve the immunosuppressive response of Tregs in different pathological conditions.

Specifically, the project will investigate the role of enzymes involved in phospholipid remodeling through the Land’s cycle, LPCAT3 and PLA2, previously identified by the PI’s team, on Treg plasma membrane composition and immunosuppressive potency. This will be achieved by combining in vitro and in vivo phenotypic and functional analyses under physiological and diseased conditions (cancer, autoimmune, and cardiometabolic diseases), with transcriptomics and lipidomics analyses. The integration of these data will provide a comprehensive picture of the Treg immunometabolic phenotype and identify the metabolic signature associated with Land’s cycle remodeling that affects Treg biology.

Finally, the knowledge acquired in the first part of the project will be exploited to pharmacologically modulate Treg function and test whether modulation of phospholipid metabolism would offer a superior immunosuppressive control of inflammation in cancer, autoimmune, and cardiometabolic diseases.

• Planned secondments

Luciana Berod lab (University Medical Center of Mainz, Germany)
• In vitro and in vivo Treg immunomodulation
• Mouse models of autoimmunity and cancer

Lemonciel lab (Biocrates, Austria)
• Metabolomics
• Algorithms for data analysis and interpretation

Thekla Cordes lab (Technical University of Braunschweig, Germany)
• In vivo metabolomics
• Mass spectrometry

• Required skills

Master’s degree in the biomedical area including Biology, Biochemistry, Biotechnology, Experimental Medicine, and Pharmacy. Knowledge of cellular and molecular biology, including immunology, is highly required. The candidate must possess excellent oral and written English skills and be proficient in drafting scientific reports based on experimental findings.

• Desirable skills

Experience with cellular, biochemical, and metabolic assays is highly preferred. A high level of flexibility, scientific curiosity, and dedication to overcoming challenges is essential. The role requires a highly organized, precise, and methodical approach to work, and a willingness to take responsibility and collaborate effectively within a team