The Laboratory of Laboratory Structural Biology https://shorturl.at/3inoD at the International Institute of Molecular and Cell Biology in Warsaw, headed by Prof. Matthias Bochtler is looking
for a Postdoctoral Researcher.
You will join the project entitled ““Stealth” asparaginases as improved protein drugs for the treatment of childhood acute lymphoblastic leukemia” carried out as the Opus grant (2024/53/B/NZ1/01841)
of the National Science Centre, Poland led by prof. Matthias Bochtler.
The ideal candidate should be able to pursue challenging tasks, achieve objectives and collaborate with other researchers. Candidates will be selected in an open competition according to the procedure complying with the rules of the European Charter for Researchers and the Code of Conduct for the Recruitment of Researchers as a part of HR Excellence in Research Strategy https://shorturl.at/f2CpW and according to the procedures defined by the National Science Centre.
The deadline for applications is 22.04.2025. Start of employment is 01.06.2025 or as soon as possible.
The project aims to apply inverse folding tools based on Large Language Models (LLMs) or Denoising Diffusion Probabilistic Models (DDPMs) combined with immune prediction tools (MHCIIpan) to design asparaginases that are expected to be less immunogenic for a given haplotype than the clinically used wild-type proteins. The asparaginases will be expressed in E. coli cells, engineered to select for high asparaginase activity. To select asparaginases in high-throughput manner, input and selected plasmid pools will be sequenced to identify the most enriched and therefore presumably most active variants among the designed proteins. Finally, the predicted and actual immunogenicity of designed asparaginase variants will be compared in a mouse model of asparaginase treatment, using standard immunological readouts and experimentally quantify the extent of the induced immune response.
As a postdoctoral researcher you will be responsible for the generation of E. coli reporter strains to test asparaginase activity with millimolar and micromolar Kd (together with the IIMCB Core Facility Unit), for the generation of large libraries of mutagenized or designed asparaginase open reading frames (based on high high-density oligo arrays to assemble synthetic genes), for the selection of optimal asparaginases using the reporter strains (this work will involve Nanopore sequencing of input DNA libraries and of DNA libraries that have been recovered from reporter strains), and for the in vitro characterization of the best enzymes. You will also collaborate on the design of candidate “stealth” enzymes, and on the characterization of the asparaginases in a mouse model of asparaginase hypersensitivity, which will be the primary responsibilities of another researcher and a PhD student.
Requirements for the candidate:
What we offer:
Selection criteria:
· Clarity and impact of motivation letter.
· Communication and teamwork abilities.
· Organizational and time-management skills.
· Compatibility with the research group goals and vision.
How to apply:
If you have questions please email mbochtler@iimcb.gov.pl or honorata@iimcb.gov.pl.
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