Regulatory mechanisms of C2-WW-HECT E3 ubiquitin ligases and the role of protein-protein interactions in their regulation

PhD Programme

RNDr. Veronika Obšilová, Ph.D.

RNDr. Veronika Obšilová, Ph.D.

The Institute of Physiology of the Czech Academy of Sciences

About us

The PhD programme at the BIOCEV Centre facilitates postgraduate studies in the fields of biotechnology and biomedicine. Multiplicity of laboratories with diverse backgrounds have found home in the BIOCEV Centre, belonging namely to the two faculties of the Charles University (1st Faculty of Medicine and Faculty of Science) and the Institute of Biotechnology of Czech Academy of Science (CAS), as well as laboratories of five other CAS institutes - the Institute of Molecular Genetics, the Institute of Microbiology, the Institute of Physiology, the Institute of Experimental Medicine, and the Institute of Macromolecular Chemistry. All these combined create the BIOCEV Centre.

In addition to their research work, the scientific and professional staff of the BIOCEV Centre directly supervise PhD students, of whom over 150 currently work at BIOCEV, and are also involved in the education of both undergraduate and graduate students. In more than 50 laboratories at the BIOCEV Centre, students learn experimental techniques and scientific methodologies under the guidance of experienced experts, which they may apply in a wide range of professional scientific work.

The aim of postgraduate training is not only to deepen knowledge in the chosen field, but also to acquire practical laboratory skills, including planning, conducting and evaluating a scientific experiment, writing scientific publications or student research projects. Similarly important is learning to present one's own scientific results and, last but not least, to develop critical thinking skills.

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If some of the open PhD positions has caught your interest and you have also found agreement with your future supervisor, you need to submit a formal application for PhD studies in Biomedicine (usually by the end of April) and then successfully pass the admission interview in front of the PhD committee (usually during June).

Accepted PhD applicants begin their studies within their chosen Biomedical PhD programme, based either in the Faculty of Science or one of the Charles University's medical faculties. Although the selected PhD programme may slightly differ in its specific requirements, all the incoming PhD students must, in coordination with their supervisor, develop an individual study plan consisting of lectures, courses, and presentations at conferences (either student, national or international level). Similarly, one hones his/her skills in preparation and submission of manuscripts and, last but not least, passing the PhD examination in front of the supervisory committee.

PhD studies are usually four years long (maximum is nine years) and are funded partly by a PhD scholarship from the relevant faculty and partly by an employment contract with the supervisor's department. Successful completion of the PhD programme requires at least one first-author publication in a peer-reviewed journal with an appropriate impact factor (or multiple co-authored publications) and a successful defense of the PhD thesis. However, the specific obligations are described by the respective disciplinary boards that organize the individual fields of study.

Regulatory mechanisms of C2-WW-HECT E3 ubiquitin ligases and the role of protein-protein interactions in their regulation

Nedd4-2 is a HECT E3 ligase that plays a critical role in pathophysiology by regulating multiple substrates, including the epithelial sodium channel (ENaC). Pathological consequences of Nedd4-2 dysregulation include respiratory distress, hypertension, electrolyte imbalance, and kidney disease. In addition to the not yet fully elucidated Ca2+ -dependent regulation of Nedd4-2, Nedd4-2 is regulated via phosphorylation and binding to various binding partners including scaffolding proteins 14-3-3. 14-3-3 proteins have the ability of binding the functionally different signal proteins, including kinases, phosphatases and transmembrane receptors by changing their function.

The aim of this project is to elucidate the regulatory mechanism human (Smurf1, Nedd4L), yeast (Rsp5) HECT E3 ubiquitin ligases and to understand the role protein-protein interactions in their regulation. For this purpose, the structure of Nedd4L, Smurf1, Rsp5 complexes with different binding partners (ClC-5, 14-3-3 proteins, arrestins) will be studied using integrative structural biology methods, in particular cryo-EM, SAXS, H/D exchange coupled to MS and chemical crosslinking coupled to MS. The structure of these complexes will be solved by combining the results of experimental methods and methods of structural bioinformatics (if needed).

The activity of E3 ligases will be measured using liposome-binding, pulse-chase and autoubiquitination assays. Combined, these approaches will allow us to elucidate regulatory mechanisms of Nedd4-like E3 ubiquitin ligases. This is a project in the field of structural biology and biophysical chemistry of proteins and is funded by grants from the research group. Cooperation with the Faculty of Science, Charles University in Prague.

Application form

The first step is to choose the PhD project(s) with the laboratory(-ies) where the PhD candidate would be interested in performing the PhD studies. Next, the candidate fills-in the online Application Form below and submits it. The completed application form will be received by the PhD project supervisor(s), who will then, at their discretion, contact the PhD candidate to discuss the next steps (e.g. online interview, etc.). Upon finding mutual interest, the candidate will then, in agreement with the project supervisor, submit a formal application for a PhD programme to the relevant university board, where the PhD applicant later undergoes admission interview for the PhD studies (usually in June).

The deadline for submitting the application within the BIOCEV Centre is 28th of February 2024, after acceptance to the selected project it is necessary to submit the application for the relevant PhD programme by 30th of April 2024 in the case of faculties of Charles University.

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Contacts

RNDr. Ladislav Anděra, CSc. RNDr. Ladislav Anděra, CSc.

RNDr.
Ladislav Anděra, CSc.

PhD Program Coordinator

ladislav.andera@ibt.cas.cz
+420325873796
Mgr. Petr Solil, DiS. Mgr. Petr Solil, DiS.

Mgr.
Petr Solil, DiS.

Head of Communications and Spokesperson

petr.solil@ibt.cas.cz
+420325873143
RNDr. Kristýna Pimková, Ph.D. RNDr. Kristýna Pimková, Ph.D.

RNDr.
Kristýna Pimková, Ph.D.

Research Associate & Deputy Head

kristyna.pimkova@lf1.cuni.cz
+420325873026