Doctoral student position with a doctoral grant in Understanding RNA transfer into cells using exosomes and lipid based nanoparticles - Hiring in process/Finished, not possible to apply

A doctoral position is an available doctoral education project to which a PhD student is to be recruited. After the selection process the process for admission to doctoral education will commence. An admission decision will not be taken until an individual study plan has been approved by the departmental admission board. For more information regarding doctoral (PhD) education, see: http://www.ki.se/doctoral. 

Research group
The Department of Laboratory of Medicine, located in Huddinge Campus, is one of the Karolinska Institutet’s largest departments with 9 research divisions including the Clinical Research Centre (CRC), where the project will be carried out. 350 people are employed at the department, half of which are PhD-students. The Centre provides the facilities needed for cell- and molecular biology research and the possibility to perform research in vivo.

Our research efforts in 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 
We are in the process of recruiting biologists, chemists and physicists on a PhD level to an interdisciplinary industrial research centre aimed at addressing next generation drug development.

The rapid development of RNA and other oligonucleotide drug modalities is about to entirely change the drug discovery arena. But with these promising high molecular weight drug candidates we are also facing new and challenging problems; discovery and development of functional delivery solutions for RNA-based drugs is of importance for clinical success. To meet this challenge, the Swedish Foundation for Strategic Research (SSF) has decided to invest in eight years of interdisciplinary and intersectional research. This has resulted in the foundation of FoRmulaEx – an industrial research centre (IRC) for functional RNA delivery. Headed by Chalmers University of Technology and with AstraZeneca as the lead industrial partner, the centre, which also includes Gothenburg University, Karolinska Institutet and additional partner companies, will enable academic research to bridge existing knowledge gaps and drive innovation in this area of high interest. Our goal is to create fundamental knowledge and novel technologies that will allow successful translation of RNA modalities into the clinic. This is thus a unique opportunity to work in a scientific and engineering area of great importance in a novel setting with industry and excellent calibre academic groups from various disciplines working hand in hand.

This particular PhD-project will mostly revolve around understanding the uptake mechanisms of bioengineered extracellular vesicles (EVs) loaded with various RNA cargoes. EVs are natural carriers of various macromolecules and play a central role in intercellular communication by conveying such cargoes to recipient cells. By understanding and exploiting them for RNA delivery, we aim to improve existing delivery modalities to allow for therapeutic RNA delivery

Most of the research will be conducted utilizing cell lines. The first part of the work will involve engineering of exosomes with fluorescent proteins and RNAs in order to quantify and visualize cellular uptake. Second part will involve understanding the underlying factors driving cellular uptake and how functional delivery of RNA cargos in exosomes can be improved.

A PhD-thesis at Karolinska Institutet encompasses 4 years full-time studies. Further information regarding the post graduate education can be found on http://www.ki.se/doctoral. Registration and the PhD-thesis will start in the autumn of 2017. 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: cloning, expression and purification of recombinant proteins, fluorescent/confocal microscopy, protein analysis (Western blot, ELISA and IP), cell culture work, purification and quantification of extracellular vesicles, and RNA expression analysis (rtPCR, qPCR and ddPCR).

It is essential that the applicant has previous experience from work with exosomes, especially in relation to RNA characterisation and delivery. 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 for doctoral education at KI
To be eligible for doctoral education following requirements has to be met:

General entry requirements
A person meets the general entry requirements for doctoral/third-cycle/PhD education (according to Higher Education Ordinance Chapt 7, section 39) if he/she:

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

Specific entry requirements
Proficiency in English equivalent to the course English B/English 6 at Swedish upper secondary school:
Proficiency in the English language can be documented by an internationally recognized test such as TOEFL or IELTS, see web-link below for more information.
Applicants who meet the general entry requirements (1 or 2 above) from a university in one of the Nordic countries fulfill the requirements in English.

For more information regarding general and specific entry requirements: http://ki.se/en/education/entry-requirements-eligibility-for-doctoral-education

Assessment criteria
A selection will be made among qualified applicants on the basis of the ability to benefit from doctoral education. Karolinska Institutet uses the following bases of assessment:
- Documented subject knowledge of relevance to the area of research
- Analytical skill
- Other documented knowledge or experience that may be relevant to doctoral studies in the subject

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

Terms and conditions
All doctoral students at KI receive financial support during their doctoral education and employment on a doctoral studentship is the most common sort of support. During the time between recruitment and admission a short-term employment can be offered for up to 6 months.

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

• A personal letter and curriculum vitae
• A copy of degree certificates and associated certificates
• A copy of degree projects and any previous publications

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