Oferta TFM | ID 33

Primary cilia are cell type-specific antennae whose transduction of chemical, mechanical or optical signals is essential for human embryonic development and postnatal life. Cilia-dependent processes in our bodies include, among others: vision, hearing, smell, cognition, motor control, kidney function, food intake, and the development of skeleton, heart and nervous system.

Ciliopathies are genetic diseases caused by cilia malfunction. Most ciliopathies are rare diseases affecting multiple organs. This is the case of Joubert-Boltshauser syndrome (JBTS), which affects 1 in 100.000 people and is associated with motor and cognitive deficits, kidney disease, retinal degeneration, and polydactyly. JBTS can be caused by mutations in at least 40 different genes, all of which encode proteins implicated in ciliary function (JBTS1-40).

About half of these proteins are required for the ciliary accumulation of INPP5E (a.k.a. JBTS1), a phosphoinositide phosphatase that controls ciliary composition, stability and signaling. However, how INPP5E functionally relates to the other half of JBTS proteins remains unclear. We have recently discovered an important clue in this regard: in common with other JBTS proteins, INPP5E regulates how ciliary microtubules are posttranslationally modified, a process also known to affect cilia stability and signaling. We are now exploring how INPP5E cooperates with other JBTS proteins to promote these ciliary functions, and how these processes go awry in JBTS. You can help us clarify these mechanisms by joining our lab for your TFM.

If you are interested, please contact us:Francesc García Gonzalo (francesc.garcia@uam.es).

Some lab publications:

• Barbeito et al. (2023) Front. Cell Dev. Biol. 11: 1190258.
• Cilleros-Rodriguez et al. (2022) eLife. 11: e78383.
• Barbeito et al. (2021) Life Sci. Alliance. 4: e202000746.