Characterisation of telomere-binding proteins

2 PhD projects offered in the IPP winter call 2020/2021

Scientific Background

Telomeres, the protective cap of chromosomes, are implicated in various biological processes including ageing and cancer development. In most differentiated cells, telomeres gradually shorten with each cell division, defining the proliferative capacity of a cell and upon reaching a limit, short telomeres ultimately induce cellular senescence. This end replication problem is counteracted in germ and stem cells by de novo addition of telomeric repeats enabled by the enzyme telomerase (also sometimes referred to as the immortality enzyme). This process it tightly regulated by telomere-associated proteins. In the last years, we have described new telomere-binding proteins like HMBOX1 (HOT1), ZBTB48 (TZAP) and ZBTB10 in human, TelAP1 in trypanosomes as well as TEBP-1 and TEBP-2 in C.elegans.

PhD project: Characterisation of telomere-binding proteins 

We are looking for a highly motivated student with a firm interest in telomere biology. A strong sense of responsibility and the ability to work independently is required. We provide the opportunity to use diverse cell biological and biochemical methods during the project. For this project, you will obtain additional support and training by several core facilities (e.g. cytometry, histology, microscopy, genomics, proteomics and bioinformatics).

We aim to extend the molecular characterization of telomeric candidates in our models S.pombe, C.elegans and zebrafish. During this project, we will establish transgenic as well as CRISPR-Cas knock-out strains to study the effect of proteins in vivo. We will apply state-of-the-art omics techniques (ChIP-seq, transcriptomics and proteomics) to obtain a global picture of gene regulation comparing germ line specific and somatic regulatory functions. Specific assays will be employed to investigate telomere length (teloblot, qFISH), effects on telomerase action (qTRAP) as well as telomeric localization (live, confocal and superresolution microscopy). Additionally, biochemical in vitro studies will supplement the in vivo analysis..

Publications relevant to the project

Dietz S, Almeida MA, Nischwitz E, Schreier J, Viceconte N, Fradera-Sola A, Renz C, Ceron-Noriega A, Ulrich HD, Kappei D, Ketting RF, Butter F. [2020] The double-stranded DNA-binding proteins TEBP-1 and TEBP-2 form a telomeric complex with POT-1. doi: doi.org/10.1101/2020.08.19.256388

Bluhm A, Viceconte N, Li F, Rane G, Ritz S, Wang S, Levin M, Shi Y, Kappei D, Butter F. [2019] ZBTB10 binds the telomeric variant repeat TTGGGG and interacts with TRF2. Nucleic Acids Res.; 47:1896-1907. 

Reis H, Schwebs M, Dietz S, Janzen CJ, Butter F. [2018] TelAP1 links telomere complexes with developmental expression site silencing in African trypanosomes.Nucleic Acids Res.; 46:2820-2833. 

Jahn A, Rane G, Paszkowski-Rogacz M, Sayols S, Bluhm A, Han CT, Draškovič I, Londoño-Vallejo JA, Kumar AP, Buchholz F, Butter F, Kappei D. [2017] ZBTB48 is both a vertebrate telomere-binding protein and a transcriptional activator. EMBO Rep; 18:929-946. 

Li JS, Miralles Fusté J, Simavorian T, Bartocci C, Tsai J, Karlseder J, Lazzerini Denchi E. [2017] TZAP: A telomere-associated protein involved in telomere length control. Science; 355:638-641.

Kappei D, Butter F, Benda C, Scheibe M, Draškovič I, Stevense M, Novo CL, Basquin C, Araki M, Araki K, Krastev DB, Kittler R, Jessberger R, Londoño-Vallejo JA, Mann M, Buchholz F. [2013] HOT1 is a mammalian direct telomere repeat-binding protein contributing to telomerase recruitment. EMBO J.; 32:1681-701.

 

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