9.2. 2022, Membránový transport

Laboratory name: Membrane Transport

Project supervisor: Olga Zimmermannová, Ph.D. (olga.zimmermannova@fgu.cas.cz)

PhD project: Identification of new regulatory mechanisms important for the maintenance of monovalent cation homeostasis in eukaryotic cells

The tight regulation of intracellular ion concentrations is crucial for all living cells. All types of cells employ various types of cation importers and exporters to ensure the optimal high levels of indispensable potassium, low levels of toxic sodium cations, and stable intracellular pH. Disordered performance of ion transporters and, consequently, non-optimal ion homeostasis result in many pathological processes. Cation/H+ exchangers (CPA/SLC9 family) belong among cation-transport systems that help to ensure the optimal intracellular levels of alkali-metal cations and protons (pH) in cells of most organisms (from bacteria to humans). The PhD project will study cation/H+ exchangers from eukaryotic cells (yeasts and mammals) with the aims of (i) determining new structural and functional elements in these proteins, (ii) unravelling new mechanisms of their regulation, and (iii) identifying so far unknown proteins that participate in their biogenesis and degradation. Obtained results will help to uncover cation-transport mechanism across membranes at the molecular level and will provide new insights into the cell cation-homeostasis regulatory network both in lower and higher eukaryotes.

Candidate’s profile (requirements):

The candidate should be highly self-motivated with master's degree or equivalent (obtained before October 2022) in molecular biology, biochemistry, microbiology or related fields. Fluent English, as well as some experience in basic laboratory (PCR, DNA and protein electrophoresis, bacteria transformation, plasmid isolation) and basic bioinformatics (DNA and protein sequence search and comparison, sequenced fragments analysis, plasmid and primers design) techniques are necessary.

References:

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.

Albacar M et al. The Toxic effects of Ppz1 overexpression involve Nha1-mediated deregulation of K+ and H+ homeostasis. J. Fungi 7(12):1010 (2021); doi: 10.3390/jof7121010.

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 Res. 1866: 118534 (2019).

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).