Doctoral (PhD) student position in extracellular vesicle-based research - Hiring in process/Finished, not possible to apply

The Department of Laboratory Medicine, located in Huddinge Campus, is one of the Karolinska Institutet’s largest departments with 7 research divisions including Biomolecular and Cellular Medicine (BCM), where the project will be carried out. 350 people are employed at the department, half of which are PhD-students.

The Division of Biomolecular and Cellular Medicine (BCM)

BCM consists of several research groups and core facilities. Activities are translational in nature and include fundamental molecular cell biology studies, pre-clinical testing of therapy/diagnostic agents and related activities, certified production of cell products for clinical use, phenotypical analysis of cells and tissues as well as clinical studies of patients treated with cell therapy agents.

Our research efforts in Associate Professor Samir EL Andaloussi´s lab focus on one of the greatest challenges facing modern therapeutics; delivery. Despite the unprecedented knowledge of diseases and their mechanisms due to advances in biomedical sciences; many promising therapeutic approaches are still clinically unavailable. This is simply because there is no efficient means of delivering these therapeutics to the right organ with the right dose. Such therapeutics include proteins for replacement therapy or antibodies for anti-inflammatory treatment as well as nucleic acids for gene therapy of diseases including muscular dystrophies and neurodegenerative disorders. We develop innovative drug delivery technologies that are able to carry protein and/or gene therapies to the target tissues safely and efficiently. We have developed a promising technology based on reprogramming exosomes, which are vesicles that are naturally used by cells to communicate, to carry therapeutic proteins and nucleic acids. We engineer exosomes with enhanced delivery and targeting capacities and screen our wide array of exosome designs in disease-relevant cellular and animal models. We are also developing methods for large-scale production and purification of such exosome therapeutics. Additionally, our lab develops methods for gene therapy based on modified cell-penetrating peptides that are efficient carriers of nucleic acids and proteins across biological barriers. We test our different technologies in models of inflammatory diseases as well as neurodegenerative and neuromuscular disorders. Our main aim is to one day unlock the potential of protein and gene therapy of such diseases by the development of novel and efficient delivery technologies.

The doctoral education project and the duties of the student

The aim of this doctoral project is to sort therapeutically relevant amounts of shRNA into extracellular vesicles (EVs) in situ and to achieve functional delivery to recipient cells.

RNA-interference offers an immense therapeutic potential, which can thus far not be fully exploited due to limitations in bioavailability. These limitations are largely determined by the properties of the delivery vehicle. To address this issue, we propose the use of highly versatile extracellular vesicles to deliver therapeutically relevant amounts of short-hairpin RNA to recipient cells in vivo. Instead of administering the EVs directly we aim to genetically instruct liver cells to produce their own biologically active EVs, which can then travel to and exert a therapeutic function in distant cells.

The first part of the doctoral project revolves around investigating endogenous strategies for functional delivery of shRNA by EVs in vitro. The second part will focus on formulating lipid nanoparticles that contain instructions for in situ production of shRNA-laden EVs. The targeted therapeutic potential of these EVs will ultimately be assessed in a tumor model in vivo.

A PhD-thesis at Karolinska Institutet encompasses 4 years full-time studies. Further information regarding the post graduate education can be found on Doctoral education. Prospective candidates should be highly motivated with the ability to work independently and as part of a team.

The applicants should have a solid background in cell biology, molecular biology or bioengineering. Practical lab experience is essential, especially in the following areas: molecular cloning methods, cell culture work, production and purification of extracellular vesicles, flow cytometry, protein analysis (Western blot), and RNA expression analysis (RT-qPCR).

It is essential that the applicant has previous experience from work with EVs. In addition, excellent proficiency in both spoken and written English is essential. We are looking for an energetic and passionate person who fits in, and actively contributes to our team.

Entry requirements

To meet the general entry requirements for third-cycle studies, an applicant must have

1. taken a second-cycle qualification

2. completed course requirements for at least 240 higher education credits, including at least 60 second-cycle higher education credits, or

3. otherwise acquired essentially the same knowledge in or outside Sweden.

Furthermore, English proficiency is required, for details see  English language requirements for doctoral education.

A selection will be made among qualified applicants on the basis of the ability to benefit from third-cycle studies. Karolinska Institutet uses the following bases of assessment:

- Documented subject knowledge of relevance to the area of research

- Analytical skills

- Other documented knowledge or experience that may be relevant to third-cycle studies in the subject

The qualifications of the applicants will be evaluated on an overall basis.

A decision concerning the doctoral student position will be made after admission to third-cycle studies. For additional information about third-cycle studies at Karolinska Institutet, see Doctoral education.

Application process

An application must contain the following documents in Swedish or English:

•            A personal letter and curriculum vitae

•            A copy of a degree certificate and associated certificates

•            A copy of a degree project and previous publications, if any

The application is to be submitted on Varbi system.