Results of the competition:
2019.09.19 raport komisji konkursowej – adiunkt naukowy – Ł. Markiewicz As part of the conducted procedure, the Competition Committee recommended the candidacy of dr Łukasz Markiewicz for this post.
Title of the position: Post-doc
Scientific discipline: Biology
Job type: Contract
Number of job offers: 1
Remuneration/Stipend amount/month: 7500 PLN gross/month
Position starts on: 01/12/2019
Maximum period of contract/stipend agreement: 36 months
Institution: Laboratory of Bioorganic Chemistry
Project leader: Paweł Sikorski
Project title: Towards understanding the cellular fate of exogenously delivered mRNA
Project Description: Exogenously delivered messenger RNA (mRNA) is a promising therapeutic agent with potential uses in cancer immunotherapies, gene therapies, and cell reprogramming. Despite clear advantage of using mRNA over DNA (e.g. mRNA does not integrate with the genome or has not to be delivered to the cell nucleus) several limitations must be overcome before mRNAs can be considered as therapeutic agents. Recently, much effort has been made either to improve cellular instability and to increase translational properties of in vitro transcribed (IVT) mRNA in complex cellular environment. However, there is also additional issue which is currently extensively studied, how immunogenic properties of IVT mRNA could modulate cell immune response. It is well known that exogenous RNA (e.g. RNA viruses) is recognized as non-self RNA and triggers cell immune defence. Key for this recognition are differences in methylation status of mRNA 5’ end. In higher Eukaryotes mRNAs bear cap-1 or cap-2 structure thus RNAs with triphosphate group or with cap-0 structure are recognized as non-self RNAs. Studies conducted so far on the cell immune response to exogenous RNA pointed out that immunogenic properties of IVT mRNA could be of great importance in its usage as therapeutic agent. Only recently, the possibility to produce IVT mRNA with non-immunogenic cap structures (cap-1 and cap-2) became available. The methods of synthesis of cap-1 and cap-2 analogues were established in Laboratory of Bioorganic Chemistry (CeNT UW) and by others (TriLink BioTechnologies). Therefore, we proposed to decipher the principles that govern recognition of IVT mRNA as non-self RNA by cell immune system. Moreover, we plan to study interplay between methylation status of mRNA 5’ end and factors responsible either for sensing or for degradation of exogenous RNA.
Key responsibilities include:
Characterization of the cellular fate of of exogenously delivered mRNA. Identification of genes involved in sensing of exogenously delivered mRNA, generation of stable mammalian cell line, subcellular localization studies of exogenously delivered RNAs, expression and purification of recombinant proteins.
Profile of candidates/requirements:
The successful post-doc candidate will have a PhD degree in biology or related discipline, experience in cell culture technique, confocal microscopy and molecular biology techniques, an additional advantage will be recombinant protein expression and purification. Scientific achievements confirming the qualifications will be required (at least two significant publication from the period of PhD studies or previous post-doc).
curriculum vitae including a description of prior research experience; a cover letter; a list of publications and conference presentations; at least two reference contacts (with phone numbers and e-mails)
Stimulating and friendly work environment
Please submit the following documents to: Applications should be submitted by e-mail to Dr Pawel Sikorski (email@example.com) no later than 31st of August 2019 with the term “Postdoc position SONATA” as email’s topic. Following an initial screening of the applications, selected candidates will be contacted by e-mail for further recruitment steps.
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Tags: cap structure, RNA sensing, immunogenicity, in vitro transcription, RNA-seq, mRNP complexes