PHD Student no. 20/2026/ICHB/PSD

Doctorat / PhD Profil chercheur : First Stage Researcher (R1) Type de contrat : Temporary Date limite de candidature : 30 Nov 2026 - 23:59 (Europe/Brussels) Programme UE : Not funded by a EU programme Référence : 20/2026/ICHB/PSD Département : Poznań Doctoral School of the Institutes of the Polish Academy of Sciences Domaine : Chemistry

KEY WORDS: G-quadruplex, DNA aptamer, hairpin, thrombin Research topic: Modified nucleotide residues as potential tool to increase aptamer - target protein interaction Principal Investigator: dr Weronika Kotkowiak Project description: Aptamers are short, single strands of DNA or RNA that act like custom-made molecular keys. Their specific sequence tells them exactly how to fold into complex 3D shapes – some look like hairpins (such as Toggle-25t), while others form G-quadruplexes (like RE31 or RV66). It is this unique shape that allows them to bind to a target protein and switch its activity on or off. While aptamers are incredibly versatile, they face a natural limitation. They are built from only four basic building blocks (nucleotides), whereas the proteins they target are made of 20 different amino acids. This lack of chemical variety means that aptamers sometimes struggle to bind their targets tightly enough. To overcome this, scientists have begun altering these building blocks. A major leap forward involved adding modifications that mimic amino acids (like SOMA-DNA), which significantly boosted how strongly aptamers could bind to proteins through hydrophobic interactions. Inspired by these advancements, we have developed novel chemical compounds called SUNAs (Slow Off-Rate Unlocked Nucleic Acids). These modifications make the aptamer backbone more flexible, allowing it to bind to protein more effectively and stay attached for much longer. We are also exploring other ways to strengthen these connections, such as: replacement of oxygen with sulfur in the aptamer bonds or using modified sugar moieties (like 2’-fluoroarabinose) to stabilize the structure. In this project, we propose to expand knowledge regarding the usefulness of these modifications for developing variants of RE31, RV66, and Toggle-25t aptamers with enhanced affinity for target proteins. A detailed understanding of these processes and mechanisms at the molecular level could enable the design of new versions of known inhibitors, which, in turn, could contribute to the improvement of therapeutic methods Additional information: Research and doctoral theses shall be carried out within the project 2024/55/D/NZ7/02686, entitled “ Modified nucleotide residues as potential tool to increase aptamer - target protein interaction ”, funded by National Science Center PhD students shall receive a stipend in the gross amount of ca 4 900 PLN (4 300 PLN net) for the period of 22 months with possible extention up to 48 months. After the positive mid-term evaluation there is an increase of the amount of the stipend to at least 5 750 PLN gross (according to current rates). PhD students shall be subject to social insurance, pursuant to article. 6 section 1 passage 7b of the act of October 13th, 1998 on the social insurance system (Journal of Laws of 2019, item 300, 303 and 730). Possibility of using the Multisport card, group insurance, social benefits (co-financing of holiday leave, refund of tickets for cultural events).

KEY WORDS: G-quadruplex, DNA aptamer, hairpin, thrombin

Research topic: Modified nucleotide residues as potential tool to increase aptamer - target protein interaction

Principal Investigator: dr Weronika Kotkowiak

Project description:

Aptamers are short, single strands of DNA or RNA that act like custom-made molecular keys. Their specific sequence tells them exactly how to fold into complex 3D shapes – some look like hairpins (such as Toggle-25t), while others form G-quadruplexes (like RE31 or RV66). It is this unique shape that allows them to bind to a target protein and switch its activity on or off.

While aptamers are incredibly versatile, they face a natural limitation. They are built from only four basic building blocks (nucleotides), whereas the proteins they target are made of 20 different amino acids. This lack of chemical variety means that aptamers sometimes struggle to bind their targets tightly enough. To overcome this, scientists have begun altering these building blocks. A major leap forward involved adding modifications that mimic amino acids (like SOMA-DNA), which significantly boosted how strongly aptamers could bind to proteins through hydrophobic interactions.

Inspired by these advancements, we have developed novel chemical compounds called SUNAs (Slow Off-Rate Unlocked Nucleic Acids). These modifications make the aptamer backbone more flexible, allowing it to bind to protein more effectively and stay attached for much longer. We are also exploring other ways to strengthen these connections, such as: replacement of oxygen with sulfur in the aptamer bonds or using modified sugar moieties (like 2’-fluoroarabinose) to stabilize the structure.

In this project, we propose to expand knowledge regarding the usefulness of these modifications for developing variants of RE31, RV66, and Toggle-25t aptamers with enhanced affinity for target proteins. A detailed understanding of these processes and mechanisms at the molecular level could enable the design of new versions of known inhibitors, which, in turn, could contribute to the improvement of therapeutic methods

Additional information:

Research and doctoral theses shall be carried out within the project 2024/55/D/NZ7/02686, entitled “ Modified nucleotide residues as potential tool to increase aptamer - target protein interaction ”, funded by National Science Center

PhD students shall receive a stipend in the gross amount of ca 4 900 PLN (4 300 PLN net) for the period of 22 months with possible extention up to 48 months. After the positive mid-term evaluation there is an increase of the amount of the stipend to at least 5 750 PLN gross (according to current rates).

PhD students shall be subject to social insurance, pursuant to article. 6 section 1 passage 7b of the act of October 13th, 1998 on the social insurance system (Journal of Laws of 2019, item 300, 303 and 730).

Possibility of using the Multisport card, group insurance, social benefits (co-financing of holiday leave, refund of tickets for cultural events).

Where to apply Website https://system.erecruiter.pl/FormTemplates/RecruitmentForm.aspx?WebID=a713cc8bf…