Postdoktor med inriktning på transtyretinamyloidos - Befattningen är under tillsättning eller redan tillsatt, och det är inte längre möjligt att lämna in en ansökan

Forskargrupperna Anders Olofsson (inst. medicinsk biokemi och biofysik) och Intissar Anan (inst. folkhälsa och klinisk medicin) söker en postdoktor som under två års heltidsarbete ska fokusera på transtyretinamyloidos. Forskningsarbetet sker i en internationell miljö. Beskrivning av projektet och arbetsuppgifter är därför formulerade på engelska. 

A main focus is to investigate the ability to inhibit production of transthyretin (TTR) in the eye by the CRISPR/Cas9 technique. The project will also involve multivariate analysis of biomarkers from patient samples as well biochemical and biophysical studies on to elucidate its interfering mechanism with other amyloid-forming polypeptides such as amyloid β, involved in Alzheimer’s disease and IAPP/amylin, linked to development of diabetes type II.

Projects
Amyloid formation resulting in depositions of protein fibrils in various tissues is a characteristic feature of in total 29 different human disorders including Alzheimer’s disease (AD), diabetes type II and familial amyloidosis with polyneuropathy. Amyloid disorders is in essence caused by an imbalance between the pathological self-assembly and clearance of the formed aggregates. Many different factors are however known to affect this balance and the cause should be considered multifactorial. A striking notion is that also very small alterations in this equilibrium can be detrimental and that a delicate balance separates healthy individuals from developing the disease. Amyloid formation from TTR is linked to a few disorders with similar pathology including familial amyloidosis with polyneuropathy, familial amyloidosis with cardiomyopathy and senile systemic amyloidosis. TTR however belongs to one of the few amyloid disorders where efficient treatments today can be offered. These includes either stabilization of the protein using small-ligands, which reduces its ability to form amyloid, as well as reducing the actual protein expression using RNAi based techniques targeting the liver which represents the main source of TTR production in the body. TTR is however also expressed in the restina of the eye and here amyloid deposits frequently results in opacities and reduced vision of the affected individuals. Current therapeutics cannot reach the retina of the eye and an aim with this project is to investigate the possibility to use CRISPR/Cas9 technique to knock-down production of TTR in the eye and hence eliminate the local protein production. If successful this would result in a single use treatment that effectively would block further amyloid formation.

Interestingly, TTR also displays anti-amyloidogenic features which raise the question about its physiological role in vivo apart from its known function as a transport protein for thyroxine-hormone and retinol binding protein. A part of the project will be focused on the interaction between TTR and amyloid-β (Aβ) linked to Alzheimer’s disease as well as the interaction between TTR and the islet amyloid polypeptide (IAPP) linked to development of diabetes type II. Here the aim is to elucidate the properties of TTR required for its amyloid interfering properties. The techniques involves protein and peptide purification, fluorescence studies to monitor amyloid formation and the probing of protein interactions using surface plasmon resonance.

Responsibilities

You will:

1. Handle animals including analysis of gene-expression using RT-PCR techniques and immune-based techniques for protein analysis.  
2. Perform protein and peptide purification and aggregation studies based on thioflavin fluorescence. 
3. Perform statistical calculations on mass spectrometric data sets and perform downstream bioinformatic analyses including pathway and enrichment analyses.
4. Participate and contribute to scientific group meetings involving the groups and their collaborators.
5. Contribute as appropriate to the publication of research findings.
6. Participate in training and supervision of scientists and research students in the group
7. Comply with the University’s Equal Opportunities and Data Protection policies.

Selection criteria

Essential

• PhD degree completed no more than 3 years ago focused on molecular biology and protein chemistry.
• Excellent written and oral English communication skills.
• Significant experience in working with animals.
• Significant experience in different molecular biology techniques
• Experience within protein misfolding and protein aggregation studies. 
• Ability to work as part of a team as well as independently.
• Ability to deliver results to required standard and schedule and to organize and prioritize own work in an independent manner.

Desirable

• Previous practical experience with generating specific sequences in the genome
• Experience in SPSS data processing and R programming.
• Experience in misfolding proteins.

Qualification Requirements for appointment as Post-doctor

A person who has been awarded a doctorate or a foreign qualification deemed to be the equivalent of a doctorate shall be qualified for employment as a post-doctor. Priority should be given to candidates who have completed their doctoral degree no more than three years before the closing date of the application. A candidate who has completed their degree prior to this may be considered if special circumstances exist. Special circumstances include absence due to illness, parental leave or clinical practice, appointments of trust in trade union organizations or similar circumstances. Post-doctors who are to teach or supervise must have taken relevant courses in teaching and learning in higher education.

Research environment

We are working in an international environment at the Department of public health and clinical medicine and Department of Medical Biochemistry and Biophysics at Umea University, Sweden. We offer an international, stimulating and collaborative research environment, in which your scientific career development is fostered.

Annonsen ska inkludera

• Personligt brev
• CV med publikationslista
• Kopia av doktorsexamen
• Kontaktinformation till 2 eller 3 referenter

https://www.umu.se/en/research/groups/anders-olofsson/

https://www.umu.se/forskning/projekt/patogenes-diagnostik-och-behandling-av-transtyretinamyloidos/

https://www.umu.se/en/wallenberg-centre-for-molecular-medicine/research/wcmm-associerade-forskare/intissar-anan/