Postdoctoral researcher in Understanding Functional RNA delivery using engineered extracellular vesicles (EVs) and lipid nanoparticles (LNPs) Full-time

Postdoctoral Researcher In Understanding Functional RNA Delivery Using Engineered Extracellular Vesicles (EVs) And Lipid Nanoparticles (LNPs)

Our research efforts in the El Andaloussi’s lab focus on one of the greatest challenges facing modern therapeutics; delivery of macromolecules to target cells in vivo. 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. Our research focus on developing novel and innovative drug delivery technologies that can carry proteins, RNAs or gene therapies to the target tissues safely and efficiently. To address this, we engineer extracellular vesicles (EVs) with enhanced delivery and targeting capacities and screen our wide array of EV designs in disease-relevant cellular and animal models. To benchmark the efficacy of engineered EVs, we also exploit established lipid nanoparticles, similar to those used in COVID-19 vaccines, for comparison. We also screen novel LNPs for improved RNA delivery capacity. Thus, our research platform offers a unique opportunity for discovering, manufacturing and delivery of advanced therapeutics.

Your Mission

As a postdoctoral research fellow, you will work on the development of bioengineered EVs and testing novel LNPs to enhance delivery of oligonucleotides and therapeutic mRNAs.

Most of the research will be conducted using cell lines and animal models. The first part of the work will involve developing stable cell lines for production of EVs engineered to harbor reporter proteins. Uptake of EVs derived from different cells will then be assessed in different recipient cells. The best EV source will then be engineered to contain mRNA or short RNAs and tested for functional delivery in relevant reporter cell lines (the reporter cell lines are already established in the lab). Successful candidate constructs will later be developed to target disease relevant targets first in vitro and later in vivo. In parallel, LNPs will be screened for delivery of splice switching oligonucleotides and mRNA therapeutics. The work will be highly innovative and require extensive knowledge regarding molecular biology techniques, cell culture and the process of making stable cells via lentivirus transduction or transposon transfection, as well as formulation work and downstream characterization of nanoparticles.

Your Profile

To be eligible for employment as a postdoctoral researcher, a PhD or a foreign degree deemed to be equivalent to a Swedish PhD is required. This eligibility requirement must be fulfilled at the latest at the time of the employment decision. Completion of your doctoral degree within the last three years is considered an advantage. If there are special reasons, your degree may have been completed earlier.

The applicant should have a solid background in basic biology and drug delivery. The position requires practical lab experience in the following areas; foremost experience with molecular engineering and isolation/characterization of EVs. Secondly, previous experience in formulation and application of LNPs and other nanoparticles for RNA delivery is critical. In addition, experience with flow cytometric analysis of protein expression and experience with PCR related techniques is required. The ideal have have experience from the EV field the applicant must hold a FELASA level animal license and have extensive experience from experimental work in rodents.

In particular, we are looking for candidates with documented expertise in:

1. EV purification: Practical expertise in EV isolation, purification, and characterization, including endogenous and exogenous loading of EVs for therapeutic or research purposes. Proficiency in purification techniques such as size-exclusion chromatography (SEC), ultrafiltration (UF), affinity-based approaches, and ultracentrifugation (UC).
2. EV characterization: Strong experience with nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and dynamic light scattering (DLS) for EV and nanoparticle characterization.
3. Microscopy and flow cytometry: Hands-on experience with microscopy and flow cytometry for cellular and EV analysis.

In addition, excellent proficiency in both spoken and written English is important. We are looking for an energetic and passionate person who fits in, and actively contributes to our team.

What Do We Offer?

A creative and inspiring environment with wide-ranging expertise and interests. Karolinska Institutet is one of the world's leading medical universities. 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. Several of the people you meet in healthcare are educated at KI. A close relationship with the health care providers is important for creating groundbreaking top quality education and research. Karolinska Institutet is also a state university, which entitles you to several benefits through our collective agreement.

Location: Flemingsberg, Huddinge

Application

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

• PhD certificate
• A complete resumé, including date of the thesis defence, title of the thesis, previous academic positions, academic title, current position, academic distinctions, and committee work
• A complete list of publications
• A summary of current work (no more than one page)

Welcome to apply at the latest 2 March.

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

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