Neuronal Proteostasis
Scientic Supervisor / Contact Person
Name and Surname
Beatriz Alvarez-Castelao
Researcher ID (link)
Other ID (link)
Localization & Research Area
Faculty / Institute
Faculty of Veterinary Medicine
Department
Biochemistry and Molecular Biology
Research Area
Life Sciences (LIF)
MSCA & ERC experience
Research group / research team hosted any MSCA fellow?
No
Research group / research team have any ERC beneficiaries?
No
Research Team & Research Topic
Website of the Research team / Research Group / Department
Brief description of the Research Team / Research Group / Department
Proteins are the dynamic molecular machines that drive the essential processes of life. Far from static, this molecular machinery constantly adapts to internal and external cues. During development, cells undergo dramatic changes in shape, location, and function—requiring a complete reconfiguration of their proteome.
Once cells reach maturity, they face two major challenges:
Maintaining proteome integrity over time through continuous protein turnover (proteostasis), and
Adapting their proteome to environmental stimuli (plasticity).
These demands are especially pronounced in neurons, where learning and memory depend on tightly regulated cycles of protein synthesis and degradation. Neurons also operate within a highly complex network of specialized neuronal and non-neuronal cells, requiring precise and context-specific proteomic control.
Disruptions in neuronal protein homeostasis—whether in synthesis or degradation—are linked to various neurodevelopmental and neurodegenerative disorders.
Our lab aims to uncover the mechanisms of protein homeostasis at cell-type resolution.
Using a selective method to identify newly synthesized proteins in defined cell types, we perform comparative proteomic studies in both wild-type and disease-related mouse models. This approach allows us to map how distinct neuronal populations remodel their proteomes under physiological and pathological conditions.
Once cells reach maturity, they face two major challenges:
Maintaining proteome integrity over time through continuous protein turnover (proteostasis), and
Adapting their proteome to environmental stimuli (plasticity).
These demands are especially pronounced in neurons, where learning and memory depend on tightly regulated cycles of protein synthesis and degradation. Neurons also operate within a highly complex network of specialized neuronal and non-neuronal cells, requiring precise and context-specific proteomic control.
Disruptions in neuronal protein homeostasis—whether in synthesis or degradation—are linked to various neurodevelopmental and neurodegenerative disorders.
Our lab aims to uncover the mechanisms of protein homeostasis at cell-type resolution.
Using a selective method to identify newly synthesized proteins in defined cell types, we perform comparative proteomic studies in both wild-type and disease-related mouse models. This approach allows us to map how distinct neuronal populations remodel their proteomes under physiological and pathological conditions.
Research lines / projects proposed
Our lab aims to uncover the mechanisms of protein homeostasis at cell-type resolution.
We employ cell-type specific in vivo approaches to investigate protein synthesis and degradation within the contexts of both neurodegenerative and neurodevelopmental disorders. Our current projects focus on:
Huntington’s disease (HD): A progressive neurodegenerative disorder characterized by polyglutamine (polyQ) expansions in the huntingtin (HTT) protein, leading to its aggregation. These aggregates disrupt cellular proteostasis and are particularly detrimental to neurons and glial cells. Using a well-characterized HD mouse model, we observe a clear progression of HTT aggregates with aging and distinct aggregation patterns between neurons and glia. This suggests differential vulnerabilities and responses in these cell types. Our research aims to elucidate the molecular pathways governing protein aggregation and clearance, focusing on the roles of the ubiquitin-proteasome system and autophagy, and how their efficiencies decline with age.
Fragile X and Rett syndromes: Neurodevelopmental disorders marked by impaired synaptic plasticity and dysregulated protein synthesis and degradation. By analyzing cell-type specific proteomes, we aim to understand how disruptions in proteostasis contribute to the pathophysiology of these conditions.
By comparing protein expression dynamics across defined neuronal populations in wild-type and disease-related mouse models, we aim to reveal how defects in proteostasis contribute to disease mechanisms and cellular vulnerability.
If you're passionate about exploring the intricate mechanisms of proteostasis and its implications in neurological disorders, we welcome you to join our collaborative and interdisciplinary team.
We employ cell-type specific in vivo approaches to investigate protein synthesis and degradation within the contexts of both neurodegenerative and neurodevelopmental disorders. Our current projects focus on:
Huntington’s disease (HD): A progressive neurodegenerative disorder characterized by polyglutamine (polyQ) expansions in the huntingtin (HTT) protein, leading to its aggregation. These aggregates disrupt cellular proteostasis and are particularly detrimental to neurons and glial cells. Using a well-characterized HD mouse model, we observe a clear progression of HTT aggregates with aging and distinct aggregation patterns between neurons and glia. This suggests differential vulnerabilities and responses in these cell types. Our research aims to elucidate the molecular pathways governing protein aggregation and clearance, focusing on the roles of the ubiquitin-proteasome system and autophagy, and how their efficiencies decline with age.
Fragile X and Rett syndromes: Neurodevelopmental disorders marked by impaired synaptic plasticity and dysregulated protein synthesis and degradation. By analyzing cell-type specific proteomes, we aim to understand how disruptions in proteostasis contribute to the pathophysiology of these conditions.
By comparing protein expression dynamics across defined neuronal populations in wild-type and disease-related mouse models, we aim to reveal how defects in proteostasis contribute to disease mechanisms and cellular vulnerability.
If you're passionate about exploring the intricate mechanisms of proteostasis and its implications in neurological disorders, we welcome you to join our collaborative and interdisciplinary team.
Key words
Application requirements
Professional Experience & Documents
We are seeking a motivated and detail-oriented scientist to join our interdisciplinary team investigating protein homeostasis at the cell-type level in the brain.
Essential Qualifications:
Bachelor's or Master's degree in Neuroscience, Molecular Biology, Biochemistry, or a related field.
Experience in molecular biology techniques (e.g., Western blotting, qPCR, immunohistochemistry).
Experience with protein extraction and analysis from brain tissue.
Good handling of mouse colonies
Strong interpersonal skills to work effectively within a multidisciplinary team.
Willingness to learn and implement new techniques and protocols.
Ability to manage multiple projects and maintain detailed laboratory records.
Genuine interest in Science
It is a plus if you: Have the ability to analyze and interpret proteomic data. Competence in using software tools for data analysis (e.g., R, ImageJ, GraphPad Prism).
What we offer:
Join to a young international team
Cutting-edge research with authorship in scientific publications.
Receive mentorship and support for career development.
Contribute to projects that have translational relevance in understanding and potentially treating neurological and neurodevelopmental disorders.
If you are enthusiastic about studying the intricacies of protein homeostasis and its implications in brain health and disease, we encourage you to apply and become a vital part of our research team!
Essential Qualifications:
Bachelor's or Master's degree in Neuroscience, Molecular Biology, Biochemistry, or a related field.
Experience in molecular biology techniques (e.g., Western blotting, qPCR, immunohistochemistry).
Experience with protein extraction and analysis from brain tissue.
Good handling of mouse colonies
Strong interpersonal skills to work effectively within a multidisciplinary team.
Willingness to learn and implement new techniques and protocols.
Ability to manage multiple projects and maintain detailed laboratory records.
Genuine interest in Science
It is a plus if you: Have the ability to analyze and interpret proteomic data. Competence in using software tools for data analysis (e.g., R, ImageJ, GraphPad Prism).
What we offer:
Join to a young international team
Cutting-edge research with authorship in scientific publications.
Receive mentorship and support for career development.
Contribute to projects that have translational relevance in understanding and potentially treating neurological and neurodevelopmental disorders.
If you are enthusiastic about studying the intricacies of protein homeostasis and its implications in brain health and disease, we encourage you to apply and become a vital part of our research team!
One Page Proposal
You can attach the 'One Page Proposal' to enhance the attractiveness of your application. Supervisors usually appreciate it. Please take into account your background and the information provided in Research Team & Research Topic section to fill in it.
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