[Neutron] mRNA therapeutics: postdoctoral position in structural characterization using neutrons, X-rays and electron microscopy

[Trevor Forsyth]

Understanding mRNA therapeutics: structural characterization using neutrons, X-rays and electron microscopy

We seek a highly motivated postdoctoral scientist with strong competence in data analysis to carry out structural analyses of a variety of mRNA lipid-based nanoparticles (LNPs) systems using small-angle scattering (SAS) techniques (both neutron and X-ray) alongside cryo-electron microscopy (cryo-EM) studies.  The position will be held in the Molecular Biophysics group in the Medical Faculty at Lund University, in close collaboration with CureVac in Germany.

The development of mRNA LNPs has intensified in the past years, particularly fueled by the SARS-CoV-2 pandemic. Beyond the treatment of COVID-19, LNP technology enables gene editing, protein replacement therapy and therapeutic cancer vaccines.  Nonetheless, there are numerous challenges associated with the formulation, delivery, and efficacy of mRNA-LNPs to date. Despite the various advancements in the field, many aspects of the structure-activity relationships in LNPs still remain to be elucidated.

CureVac, a biotechnology company based in Tübingen, Germany (https://www.curevac.com/en/), has been a pioneer in the field of mRNA research for the past 24 years. The successful delivery of mRNA in vivo is contingent on the LNP delivery vehicle. This project aims to delve into the lipid-based building blocks which make up the LNP, utilizing powerful structural tools to investigate structure-activity relationships that will enable the future efficient design of potent mRNA LNP therapeutics. CureVac has been focusing on innovations in the lipid space for the design and in vitro/in vivo characterization of novel LNPs and the identification of factors that can significantly improve potency following intravenous administration.

The project will make extensive use of synchrotron X-ray facilities such as MAX IV, ESRF, Diamond, and neutron beam facilities such as ILL, ISIS (as well as the ESS spallation neutron source which will become available during the period of the project).  Data from these facilities will be used with information from cryo-EM to establish reliable structural models associated with different types of LNPs and their variation in response to different conditions.  Where appropriate, isotope labelling will be exploited to enhance the visibility of different LNP components. The project aims to use machine learning trends to deliver reliable prediction methods for LNP morphology and content.

To apply for this position, see https://www.ambercofund.eu/for-applicants. Informal enquiries to Trevor Forsyth (trevor.forsyth at med.lu.se<mailto:trevor.forsyth at med.lu.se>).

This position is funded under the EU MCSA COFUND project on Advanced Multiscale Biological imaging using European Research infrastructures (AMBER). To read more about AMBER see https://www.ambercofund.eu. The AMBER partner organisations are Lund University, the MAX IV synchrotron radiation source, Sweden, the European Molecular Biology Laboratory (EMBL), the Institut Laue-Langevin (ILL), France, the European Spallation Source (ESS), Sweden, the International Institute of Molecular Mechanisms and Machines, (IMOL), Poland, and the Leicester Institute of Structural and Chemical Biology, UK. AMBER is coordinated by LINXS (https://www.linxs.se/).

Link to the AMBER Linkedin: https://www.linkedin.com/company/amber-postdoctoral-programme.

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