PhD - Modulating Targets, Human Neurodegenerative diseases

Combine your scientific drive with your strategic and tactical skills in a new exciting PhD position funded by the Swedish Foundation for Strategic Research, jointly supervised by the Dept of Physiology and Pharmacology, Karolinska Institutet in Stockholm, Sweden and the Translational Genomics Lab within AstraZeneca, Discovery Sciences in Gothenburg, Sweden.

The focus of the studentship is to find new ways to treat common brain disorders, which are on the rise due to increased life expectancy. Neuronal proteinopathies, characterized by the aggregation of misfolded protein, affect millions of people globally and there is a high degree of unmet clinical need. Mechanisms that protect against protein aggregation are therefore therapeutically interesting and our aim is to modulate targets, important in a range of human neurodegenerative diseases, to reduce the accumulation of protein aggregates. Alzheimer's, Parkinson's and schizophrenia are among the world's most common brain diseases and a similar basic defect is common to all three: errors in the body's ability to fold protein into the correct shape and the subsequent toxic accumulation of mis-shaped proteins. Current treatments can relieve patient symptoms, but there are no cures. Our aim in this study is to treat these disorders by developing new types of drugs aimed at reducing the amount of mis-folded protein.

The project goal is to establish the potential of proteasome activation to counteract the development of neurodegenerative disease, using mouse models of Alzheimer's, Parkinson's and schizophrenia. Specifically, the project aims to:

* Interrogate whether proteasome activation has a potential protective role in mouse models of neurodegenerative disease with altered protein expression levels of proteosome components.
* We will utilize biochemical, histological and live mouse phenotypic analysis to determine if increased levels of proteasome activation protect against protein aggregation.
* Guided by biochemical and histological findings we will determine if proteasome activation protects against protein aggregation and whether this translates to an improvement in multiple neurodegenerative phenotypes.

What you'll do:
In this role you will be part of the AstraZeneca team responsible for the development and characterization of advanced transgenic mouse models and relevant readouts (e.g. motor function and behavioural assays). You will combine your scientific knowledge expertise to deliver high quality results as a lab-based scientist and to plan, design, execute and analyse data from experiments to generate high quality results to support project decisions and milestones. As well as ensure that studies are conducted with quality and data delivered according to stipulated timelines and project requirements.You will also compile, interpret, present and discuss data within the project team. A distinct advantage would be an interest in human neurodegenerative disease and knowledge of how animal models can impact upon their pre-clinical study.

Eligibility requirements for doctoral education:
In order to participate in the selection for a doctoral position, you must meet the following general (A) and specific (B) eligibility requirements at latest by the application deadline.

It is your responsibility to certify eligibility by following the instructions on the web page Entry requirements (eligibility) for doctoral education.

A) General eligibility requirement
You meet the general eligibility requirement for doctoral/third-cycle/PhD education if you:

1) have been awarded a second-cycle/advanced/master qualification (i.e. master degree), or
2) have satisfied the requirements for courses comprising at least 240 credits of which at least 60 credits were awarded in the advanced/second-cycle/master level, or
3) have acquired substantially equivalent knowledge in some other way in Sweden or abroad.*

Follow the instructions on the web page Entry requirements (eligibility) for doctoral education.

*If you claim equivalent knowledge, follow the instructions on the web page Assessing equivalent knowledge for general eligibility for doctoral education.

B) Specific eligibility requirement
You meet the specific eligibility requirement for doctoral/third-cycle/PhD education if you:
- Show proficiency in English equivalent to the course English B/English 6 at Swedish upper secondary school.

Follow the instructions on the web page English language requirements for doctoral education.

Verification of your documents Karolinska Institutet checks the authenticity of your documents. Karolinska Institutet reserves the right to revoke admission if supporting documents are discovered to be fraudulent. Submission of false documents is a violation of Swedish law and is considered grounds for legal action.

(A) and (B) can only be certified by the documentation requirement for doctoral education.

We look forward to you receiving your application and we welcome it no later than 21st October 2022.