29.1. 2024, Laboratory of Membrane Transport

PhD project: New regulatory mechanisms of the maintenance of monovalent-cation homeostasis crucial for the health of eukaryotic cells

Monovalent cations H+, K+, and Na+ are key elements of life required for all cellular functions. The intracellular concentrations of K+, Na+, and protons (pH) are determined via the activity of membrane proteins - transporters and channels mediating the continuous flux of cations and protons into and from cells with various transport mechanisms. Using the yeast Saccharomyces cerevisiae as a eukaryotic model organism, the PhD project will study new regulatory mechanisms maintaining monovalent-cation homeostasis in cells. The results will provide new insights into the regulation of cation homeostasis on the level of (i) particular cation transporters’ proteostasis (expression, biogenesis, function, and degradation) and (ii) their distribution/organization in the plasma membrane. The identification of new interactions among transporters and regulatory proteins will significantly advance our knowledge of molecular mechanisms required to maintain cation homeostasis and their physiological importance in healthy organisms.

Candidate’s profile (requirements):

The candidate should be highly self-motivated with master's degree or equivalent (obtained before October 2024) in molecular biology, biochemistry, microbiology or related fields. Fluent English, as well as some experience in the basic laboratory (PCR, DNA and protein electrophoresis, bacteria transformation, plasmid isolation), bioinformatics (DNA and protein sequence search and comparison, sequenced fragments analysis, plasmid and primers design) as well as microscopic techniques are necessary.

Supervisor: Olga Zimmermannová, PhD. 

References:

1. Velazquez D. et al. Allosteric links between the hydrophilic N-terminus and transmembrane core of human Na+/H+ antiporter NHA2. Protein Science 31: E4460-E (2022); doi: 10.1002/pro.4460.

2. Papouskova K. et al. C5 conserved region of hydrophilic C-terminal part of Saccharomyces cerevisiae Nha1 antiporter determines its requirement of Erv14 COPII cargo receptor for plasma-membrane targeting. Mol Microbiol 115(1):41-57 (2021); doi: 10.1111/mmi.14595.

3. Smidova A. et al. The activity of Saccharomyces cerevisiae Na+, K+/H+ antiporter Nha1 is negatively regulated by 14-3-3 protein binding at serine 481. BBA – Mol Cell Re. 1866: 118534 (2019); doi: 10.1016/j.bbamcr.2019.118534.

4. Zimmermannova O. et al. Erv14 cargo receptor participates in regulation of plasma-membrane potential, intracellular pH and potassium homeostasis via its interaction with K+-specific transporters Trk1 and Tok1. BBA – Mol Cell Res 1866: 1376–1388 (2019); doi: 10.1016/j.bbamcr.2019.05.005.