Targeting of somatic hypermutation by the interplay of transcriptional kinetics and DNA repair fidelity

Organisation/Company

Institute of Molecular Genetics of the Czech Academy of Sciences

Research Field

Biological sciences
Medical sciences

Researcher Profile

First Stage Researcher (R1)

Application Deadline

28 Feb 2026 - 22:50 (UTC)

Country

Czech Republic

Type of Contract

Temporary

Job Status

Full-time

Offer Starting Date

1 Oct 2026

Is the job funded through the EU Research Framework Programme?

Not funded by a EU programme

Is the Job related to staff position within a Research Infrastructure?

No

Supervisor

Filip Šenigl

Project description

Somatic hypermutation (SHM) is a key process in diversification of antibodies. This process is initiated by cytosine deamination by the activation-induced cytidine deaminase (AID) and completed by error-prone processing of the resulting uracils. Though SHM aims primarily to Ig loci frequent targeting of non-Ig loci was reported accentuating the role of SHM in lymphomagenesis. We developed a series of novel methods providing data on SHM susceptibility in B cell genome and identifying a series of factors involved in SHM. Based on our preliminary results, we propose a model of somatic hypermutation targeting combining the roles of AID access to various genomic regions and site-specific variability of error-proneness of DNA repair. Our novel approach will decipher transcriptional kinetic features involved in targeting of AID activity and identify factors responsible for specific distribution of cytidine deamination and high error rate of DNA repair in SHM-targeted regions. Our study will provide a novel insight into the mechanism of SHM targeting and its involvement in lymphomagenesis.

The project will be demanding on establishment of various high-throughput methods (integration site libraries, ChIP-seq, RNA-seq, etc.). The project will also require extensive bioinformatic analysis which doesn’t need to be necessarily performed by the candidate, however, experience with high-throughput datasets or bioinformatic analysis is advantageous.

The project is run in very close collaboration with the laboratory of David Schatz, Immunobiology, Yale School of Medicine, CT, USA

Candidate profile

The candidate should have experience with tissue culture experiments and basic molecular biology techniques (PCR, plasmid construction) as well as basic microscopic skills. The candidate should be able to work with scientific literature and communicate in English language.

We offer

Position in well-established laboratory producing high quality science
Friendly team of collaborators
Full-time job at the Czech Academy of Sciences
Highly interesting topic with the possibility of stay in the Schatz lab at Yale university (USA)
Opportunity to learn the state-of-the-art molecular biology technique

Suggested reading

Senigl F, Maman Y, Dinesh RK, Alinikula J, Seth RB, Pecnova L, Omer AD, Rao SSP, Weisz D, Buerstedde JM, Aiden EL, Casellas R, Hejnar J, Schatz DG: Topologically Associated Domains Delineate Susceptibility to Somatic Hypermutation. Cell Rep 2019 29(12): 3902-3915.e8.
Šenigl F, Soikkeli AI, Prost S, Schatz DG, Slavková M, Hejnar J, Alinikula J: The SV40 virus enhancer functions as a somatic hypermutation-targeting element with potential tumorigenic activity. Tumour Virus Res 2024 18: 200293.
Feng Y, Seija N, Di Noia JM, Martin A. (2020) AID in Antibody Diversification: There and Back Again. Trends in Immunology, July 2020, Vol. 41, No. 7

APPLY HERE: https://www.img.cas.cz/phd

Website

https://www.img.cas.cz/phd

Number of offers available

1

Company/Institute

Institute of Molecular Genetics of the Czech Academy of Sciences

Country

Czech Republic

City

Prague

Postal Code

14200

Street

Vídeňská 1083

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