16 May 2023
Job InformationOrganisation/Company
Instituto de Investigação e Inovação em Saúde da Universidade do Porto (i3S)
Research Field
Biological sciences » Biology
Researcher Profile
Recognised Researcher (R2)
Country
Portugal
Application Deadline
15 Jun 2023 - 00:00 (Europe/Lisbon)
Type of Contract
Other
Job Status
Full-time
Hours Per Week
35
Offer Starting Date
17 May 2023
Is the job funded through the EU Research Framework Programme?
Not funded by an EU programme
Reference Number
FellowBI/FCTProj2022/i3S/17051506/2023
Is the Job related to staff position within a Research Infrastructure?
No
Offer Descriptioni3s – Institute for Research and Innovation in Health (hereinafter i3) is opening a call to award a grant for the development of R&D activities by Master's or Integrated Master's, or Bachelor's enrolled in non-academic degree courses integrated into the educational project of a higher education institution within the project “Comparative analysis of proteomics and genomics of a yeast model of N88S BSCL2/seipin-related human seipinopathy” - 2022.02305.PTDC, financed by national funds through FCT – Fundação para a Ciência e a Tecnologia, I.P.
Host Institution: i3S - Instituto de Investigação e Inovação em Saúde, Porto, Portugal.
Scientific Area : Molecular and Cellular Biology.
Project Title: “ Comparative analysis of proteomics and genomics of a yeast model of N88S BSCL2/seipin-related human seipinopathy”.
Workplans
Lipid droplets (LDs) are ubiquitous fat storage organelles composed of a core made of triacylglycerols (TG) and sterol esters (SE), and surrounded by a phospholipid monolayer membrane with some decorating proteins.
The group recently identified Ldo16 and Ldo45 proteins, orthologous to human TMEM159/LDAF1, as binding partners of seipin to form the core complex that regulates maintenance of ER-LD contact sites. Seipin is expressed in the brain and motor neurons of the spinal cord, and regulates excitatory synaptic transmission and release of synaptic vesicles. Lack of seipin results in depression-like behaviours. Interestingly, the same protein is involved in distinct clinical manifestations: Berardinelli-Seip congenital lipodystrophy type 2 (BSCL-2) and seipinopathies. BSCL-2 is characterized by a severe adipose tissue disorder caused by seipin deficiency. On the other hand, seipinopathies refer to seipin-related motor neuron diseases (MNDs), including Silver syndrome/spastic paraplegia 17 (SPG17) and distal hereditary motor neuropathy type V (dHMN-V). The two mutations that cause neuronal seipinopathy, N88S and S90L, are located within seipin´s loop, an 'aggregation-prone' segment in the protein. By disrupting N-glycosylation, these mutations promote protein aggregation and induce ER stress and cell death, a mechanism shared with other neurodegenerative disorders. Also, seipin N88S is polyubiquitinated and degraded by the proteasome. Importantly, protein aggregates accumulate into inclusion bodies (IBs). We have successfully established a yeast model of N88S seipinopathy, which recapitulates human seipinopathy cellular features, namely higher levels of ER stress during aging, and the presence of IBs associated with the formation of WT-N88S heteromers or N88S homo-oligomers, thus indicating that WT seipin can also interact with the mutant form. For the first time, the group uncovered that N88S homo-oligomers expressing cells present reduced viability linked to elevated oxidative damage promoted by higher ROS accumulation and lipid peroxidation, and crucially diminished antioxidant activity. Importantly, we observed the activation of the oxidative stress sensor Yap1, which is functionally linked to human Keap1-Nrf2 integrated redox-sensitive signaling system. In this project, we intend to use our model to uncover genes that modulate aggregation and oxidative stress, either by reducing or enhancing N88S toxicity, based on genomic screening of the commercially available yeast knockout collection. In parallel, we will employ mass spectrometry proteomics to elucidate the role of proteins and define signaling pathways contributing to these disease-related features, hopefully unveiling the molecular pathogenesis of seipinopathy in more detail. The combination of two well- established omics approaches will allow in-depth characterization of our model system of seipinopathy, and this research will work as a major stepping-stone to define the disease mechanisms and novel therapeutic targets to be translated in human model studies.
The successful candidate will develop their research work in the Yeast Signalling Group Group, focused on the proteomic characterization of the established model (differential levels of protein expression, functional characterization of mutants using different techniques of molecular biology and biochemistry and microscopy imaging) and to contribute to optimize and validate the model of seipinopathy.
Admission Requirements :
Mandatory:
Being enrolled in a Master's degree or Integrated Master's in Molecular and Cellular Biology, or related areas; Or:
Bachelor's enrolled in non-academic degree courses integrated into the educational project of a higher education institution at the time of the start of the contract.
Applicants must have a degree in Biology.
Preferential:
Preference will be given to candidates with knowledge and experience on the following techniques/methodologies:
- Molecular biology techniques (PCR, Western Blotting);
- Fluorescence microscopy and spectroscopy;
- Good teamwork and interpersonal skills
Legislation and other applicable regulations : Research Fellowship Holder Statute enacted by Law no. 40/2004 of August 18th, as amended; FCT Research Grants Regulation, approved by way of Regulation nr. 950/2019, published in the II Series of DR of December 16th, 2019; i3S Research Grants Regulation.
Place : The research activities will be hosted at i3S, under the scientific coordination of Professor Vitor Teixeira.
Length time: The duration of the fellowship is 10 months, eventually renewable. The expected starting date is the 1st of September 2023, upon availability of the financed funds.
Monthly maintenance stipend: €930,98, according to the values table of FCT, at Portugal (https: // www. fct.pt/wp-content/uploads/2023/02/Tabela-de- Valores-SMM2023.pdf). The payments will be made by bank transference.
Research grants may also include other components, as the voluntary social insurance, under the terms of the Research Fellowship Holder Statute, article 10.
Evaluation Criteria : The candidates will be assessed based on their CV (60%, considering their experience in the areas listed in the “Admission Requirements”); quality of the cover letter (15%) and interview (25%). The assessment will be graded from 1 to 100 and the candidates ranked based on their final score. Only the best three candidates, with score higher than 60%, will be invited for interviewing.
Evaluation Pannel : President - Professor Vitor Teixeira; member - Professor Vítor Costa; member - Professor Catarina Pacheco.
Information and Publicity of Funding Granted : The evaluation results will be published on the i3S website. The candidates will be notified by email. Candidates have a period of ten working days to, if they wish, to express their opinion at the prior hearing of the interested parties, by email [email protected].
Applications: The call will be open between may 17th 2023 and june 15th 2023.
The applications must be submitted electronically at:
https: // DOZER.i3s.up.pt/applicationmanagement/#/addapplications/FellowBIFCTProj2022i3S170515062023
The required documents composing the applications are: Certificate of Qualifications, Curriculum Vitae, letter of motivation, proof of enrolment in Master's or Integrated Master's study cycle or non-academic degree courses integrated into the educational project of a higher education institution or a honor statement of capacity to enroll in the aforementioned study cycle or courses until the grant is contracted, and other documents, considered as relevant by the candidate.
Documents to be provided at the time of contracting: in addition to those mentioned in the previous point, it is necessary to present proof of enrollment in Master's or Integrated Master's study cycle or non-academic degree courses integrated into the educational project of a higher education institution.
Full announcement at: https: // dozer.i3s.up.pt/fileupload/downloadfile/viewpdfnewtab/51725bebe…
RequirementsResearch Field
Biological sciences » Biology
Education Level
Bachelor Degree or equivalent
Specific Requirements
Admission Requirements :
Mandatory:
Being enrolled in a Master's degree or Integrated Master's in Molecular and Cellular Biology, or related areas; Or:
Bachelor's enrolled in non-academic degree courses integrated into the educational project of a higher education institution at the time of the start of the contract.
Applicants must have a degree in Biology.
Preferential:
Preference will be given to candidates with knowledge and experience on the following techniques/methodologies:
- Molecular biology techniques (PCR, Western Blotting);
- Fluorescence microscopy and spectroscopy;
- Good teamwork and interpersonal skills
Research Field
Biological sciences » Biology
Website for additional job details
https: // dozer.i3s.up.pt/fileupload/downloadfile/viewpdfnewtab/94fe80d292a77b9e5…
Work Location(s)Number of offers available
1
Company/Institute
i3S
Country
Portugal
Geofield
Where to applyWebsite
https: // DOZER.i3s.up.pt/applicationmanagement/#/addapplications/FellowBIFCTPr…
ContactCity
Porto
Website
https:// www. i3S.up.pt
Street
Rua Alfredo Allen 208
Postal Code
4200-135
STATUS: EXPIRED