Beatriz Alvarez Castelao

Proteins are the molecular machines that execute the complex physicochemical processes of life. This molecular machinery is dynamic and is remodelled in response to environmental changes. During development, cells undergo a massive transformation. As a consequence, they need to adapt their initial protein content to their final shape, location, and function. Once cells reach their mature state they face two distinct challenges: on the one hand they have to maintain their proteomes in a functional state over the whole lifetime by degrading and replacing proteins (proteostasis), on the other hand, they have to adapt to the environment by modifying their proteomes (plasticity). This task is especially evident in neurons where learning and memory processes require constant proteome remodelling via protein synthesis and degradation, additionally, neurons receive stimuli from an intricate network composed of very specialized neuronal and non-neuronal cells.
Aberrant neuronal protein synthesis and degradation in neurons have been related to several neuropsychiatric and neurodegenerative diseases.
The global aim of my laboratory will be to study protein homeostasis using a cell-type specific method for protein identification. We are doing comparative studies of protein expression profiles in specific cell-types, in wt and disease-related mouse models.

Proteostasis study in Huntington disease mouse model:
The motivation for choosing this model is that in this mouse line there is a clear progression of the aggregates with aging and it is a clear difference in the aggregation pattern found in different cell-types, specially two main cell-types in the brain; Neurons and Glia, both with important roles in the development of the disease.

Huntington"s disease belongs to the polyglutamine diseases, this group of neurodegenerative disorders is characterized by the expansion of the trinucleotide repeat CAG, encoding for glutamine. Polyglutamine expansions induce protein aggregation that ultimately/or simultaneously disturbs cellular protein homeostasis. The onset of the disease is proportional to the number of repeats, but generally appears in middle/elderly-aged individuals and the aggregates of Huntingtin (Htt) become more frequent with age in all cases. One possible explanation for this is that younger neurons are able to clear cytotoxic proteins more efficiently than older neurons, this might occur because the degradation machinery, including the UPS or autophagy, might become less efficient with age. Despite extensive exploration of these pathways, it remains elusive which are the specific changes on its components, or which are the specific factors that modulate Htt aggregation during the aging process. We are using cell-type specific proteomes to explore the protein landscape in neurons and glia with the aim to elucidate some of the molecules/pathways involved in protein aggregation and clearance.

Able to handle mice
able to perform routinely laboratory techniques such as WB, SDS-PAGE, IF..
if the applicant know computational programing, or protein Mass Spectrometry analysis this would be a plus.