Group of Integrated Metabolism in Immunity

Lymphocyte activation is associated with major changes in metabolism. These changes provide energy and building blocks to the cells to proliferate and to differentiate in different effector cells.

B-lymphocytes are key components of the adaptive immune response producing highly specific antibodies. In vivo, activated B cells rapidly differentiate to antibody-secreting cells or enter into germinal centers (GC) where BCR affinity maturation and class switch recombination take place. Once B cells exit the GC, they differentiate into either high-affinity antibody long-lived plasma cells or memory cells. It has been described that metabolic reprograming is important for regulating these fate decisions in B cells ^{1, 2, 3,} however, the precise function of mitochondria in the GC reaction is still unknown.

In this project the student will evaluate the role of the mitochondria function in the GC reaction, analyzing different aspects of B cell function, such as B cell activation, proliferation, antigen presentation, B cell differentiation and antibody production. For this purpose the student will use mice whose B cells lack Tfam (a mitochondria transcription factor) specifically at the GC. These cells present a mitochondria dysfunction once B cells are activated.

The student will be part of a small group with a good research atmosphere and he/she will learn a broad amount of different techniques such as cell culture, confocal microscopy, flow cytometry and ELISA among others.

1. Martinez-Martin, N. et al. A switch from canonical to noncanonical autophagy shapes B cell responses. Science 355, 641-647 (2017). 

2. Mendoza, P. et al. R-Ras2 is required for germinal center formation to aid B cells during energetically demanding processes. Sci Signal 11 (2018).

3. Tsui, C. et al. Protein Kinase C-beta Dictates B Cell Fate by Regulating Mitochondrial Remodeling, Metabolic Reprogramming, and Heme Biosynthesis. Immunity 48, 1144-1159 e1145 (2018).

Candidate requisites

1.- High motivation for research.

2.- Good academic record.