Postdoctoral researchers in “Astrocyte-to-neuron conversion for cell replacement in Parkinson’s disease”

We invite applications for a postdoctoral position in the laboratory of Professor Ernest Arenas: http://ernestarenaslab.org/. The position will be placed in the Division of Molecular Neurobiology, a cluster of 8 research groups forming a dynamic and collaborative research environment within the MBB department, at the Karolinska Institute.

Our laboratory is located in Biomedicum, one of the largest and most modern research buildings in Northern Europe, within a world leading University, Karolinska Institutet. Our lab offers an inclusive, interactive, multidisciplinary and international research work environment, where you can develop your career and make a difference.

Your mission

We look for two postdoctoral fellows interested in developing precision cell replacement strategies for Parkinson’s disease based on cell engineering. Our laboratory has previously provided proof of concept that the conversion of astrocytes into midbrain dopamine neurons in vivo can rescue motor deficits in a mouse model of PD (Rivetti di val Cervo, 2017, Nature Biotechnology). We now aim at further developing these technologies, at improving the functionality of the converted DA neurons and at understanding the reprogramming process in grater detail by using, amongst others, single cell RNA-sequencing methodologies and computational tools to ascertain the quality of the DA neurons (La Manno et al., 2016, Cell; Nishimura et al., 2022, in preparation).

Different aspects of the process of converting disease-associated astrocytes into induced midbrain dopaminergic neurons of the substantia nigra subtype, will be examined. This includes the following steps:

1) Define the molecular subtypes and the properties of astrocytes found in the brain of patients with idiopathic Parkinson’s disease (PD) and in rodent models of PD by single cell multiomics.

2) Develop viral vectors and strategies to selectively and efficiently target defined human astrocyte subtypes in vitro and mouse astrocytes in models of PD.

3) Identify factors and mechanisms by which human astrocytes in vitro and mouse astrocytes in models of PD can be converted into dopaminergic neurons of the substantia nigra subtype. This will involve the use of single cell methodologies to define the cell types, their properties and their trajectories during reprogramming. Functional genomics will be used to define the molecular mechanisms or reprogramming.

Steps 1+2 will be addressed by postdoc 1 and steps 2+3 by postdoc 2. The successful candidates will either be part of an international collaborative project supported by the EU or of a team effort supported by an ERC Advanced Grant (PreciseCell PD 2021-2026).

Your profile

You are a PhD about to defend your thesis or a Postdoctoral interested in Parkinson’s disease, astrocyte-to-neuron conversion and brain repair. You have experience in one or more of the following areas: viral vectors, gene therapy, stereotaxic surgery, anatomy and function of the basal ganglia, cell culture, molecular biology or single cell RNA-sequencing. Knowledge or experience of working on midbrain, FACS, rodent models of Parkinson’s disease, electrophysiology and rodent behavior analysis will be considered as extra merits. Previous experience of working in international environments will be advantageous. Applicants should have good communication skills and be proficient in spoken and written English.

Qualified to be employed as a postdoctor is one who has obtained a doctorate or has equivalent scientific competence. It is considered as an advantage if you have completed your doctoral degree within the last three years, if there are special reasons, your degree may have been completed earlier. Applicants who have not completed a doctorate at the end of the application period may also apply, provided that all requirements for a completed degree are met before the (intended) date of employment. This must be substantiated by the applicant’s main supervisor, director or equivalent.

What do we offer?

We offer a full time (100%) 1+1 year with possibility of extension postdoctoral position starting in September 2022. Our laboratory and our unit offer a creative, interactive and international research environment, where you can develop, enjoy science and make a difference.

The project offers excellent training opportunities, an outstanding research network and opportunities to interact and collaborate with world leading laboratories and top researchers working in the area of PD and regenerative medicine

A creative and inspiring environment with wide-ranging expertise and interests. Karolinska Institutet is one of the world’s leading medical universities. Our vision is to pursue the development of knowledge about life and to promote a better health for all. At Karolinska Institutet, we conduct successful medical research and hold the largest range of medical education in Sweden. At KI, you get to meet researchers working with a wide range of specialisms and methods, giving you ample opportunity to exchange knowledge and experience with the various scientific fields within medicine and health. It is the crossover collaborations, which have pushed KI to where it is today, at the forefront of global research. Karolinska Institutet is also a state university, which entitles you to several benefits through our collective agreement.

Location: Solna, Biomedicum

Application

Your application must contain the following documents in English:

1. A complete curriculum vitae, including date of the thesis defence, title of the thesis, previous academic positions, academic title, current position, academic distinctions, and committee work
2. A complete list of publications.
3. A summary of current work (no more than one page).
4. A letter of motivation (no more than one page)
5. Three references or reference letters
6. Verification from the thesis defence committee or the equivalent (only if the thesis defence is scheduled within three months after the application deadline).

In assessing candidates we will place our emphasis on the personal trajectory, education, technical skills, CV, merits and previous experience.

You are welcome to apply at the latest by the 15th of August 2022

The application is to be submitted through the Varbi recruitment system.

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