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Dr Zita Balklava

Supervisor Details

Dr Zita Balklava

Contact Details

Dr Zita Balklava

School of Biosciences, Aston University

Research Interests

Currently, work in my lab focuses on understanding the cross-talk of membrane trafficking and cell signalling within the cell via deciphering interactions and trafficking of several membrane proteins/receptors:

  1. Fibroblast Growth Factor Receptor (FGFR): understanding how FGFR and its downstream signalling pathways regulate membrane trafficking;
  2. Amyloid Precursor Protein (APP): dissecting physiological role of APP by studying its trafficking, the interactors of its intracellular domain and the biological consequences of these interactions.
  3. Aquaporin 4 (AQP4): identifying the key membrane transport regulators involved in trafficking AQP4 between the plasma membrane and intracellular vesicles in response to changes in osmolarity.

Recently I have established a collaboration to study the role of Stress Granules in C. elegans Alzheimer's and Parkinson's Disease models.

Scientific Inspiration

My main inspiration is my father who was a scientist and a professor. He was always supportive of my goals and natural interest in biology to explore how the world works.


Project Details

Dr Balklava is the primary supervisor on the below project:

Deciphering the role of stress response in neurodegeneration

Secondary Supervisor(s): Dr Mariaelena Repici

University of Registration: Aston University

BBSRC Research Themes:

Apply here!

Deadline: 4 January, 2024


Project Outline

Stress granules (SGs) are dense aggregations of proteins and mRNAs appearing in the cytosol under stress conditions. They are transient and dynamic structures and play a critical role in mRNA metabolism and translational control by modulating the stress response. SG formation is transient and represents a physiological response to stress, however chronic stresses associated with aging and neurodegeneration lead to formation of persistent SGs that contribute to aggregation of disease-related proteins.

SGs dynamics have been mainly studied in yeast or human cell lines and not enough information is available on stress granules in multicellular organisms. C. elegans represents a powerful model to study neurodegeneration and dissect molecular mechanisms and signaling pathways contributing to pathology. An array of established C. elegans mutants can give insight into different aspects of neurodegenerative disease pathogenesis. Similarly, several tools are now available to study the role of cytoplasmic stress granules in stress response in C. elegans.

The aim of this project is to use C. elegans models for neurodegenerative diseases (Alzheimer’s Disease (AD) and Parkinson’s Disease (PD)) to investigate stress response and SG dynamics and role in neurodegeneration in young and aging adults. This will be achieved through the following objectives: Objective 1: Analyse SG dynamics in C. elegans AD and PD models using fluorescently labelled SG markers. For this objective GFP-tagged SG markers TIAR-1 and GTBP-1 will be crossed into AD and PD mutant worms and SG dynamics will be analysed using fluorescence microscopy at different time points throughout the lifetime of the animals in the presence and absence of acute stress. Objective 2: Investigate whether modulation of SG formation affects AD and PD disease phenotypes and general worm fitness indicators. This objective will be achieved by crossing loss-of-function mutations of SG key proteins TIAR-1 and GTPB-1 into mutant AD and PD worms and analysing the resulting phenotypes at different time points throughout the lifetime of the animals. Together these objectives will allow to understand whether SGs play a crucial role in AD and PD pathogenesis and potentially suggest novel therapeutics for neurodegeneration.

References

Wolozin, B. and Ivanov, P. (2019). Stress Granules and neurodegeneration. Nat Rev Neurosci, 11, 649-666, doi: 10.1038/s41583-019-0222-5.

Van Pelt, K. M. and Truttmann, M.C. Caenorhabditis elegans as a model system for studying aging-associated neurodegenerative diseases. Translational Medicine of Aging, 4, 60-72, https://doi.org/10.1016/j.tma.2020.05.001

Techniques

  • Genetic manipulations using transgenic technologies in C. elegans.
  • C. elegans disease-related phenotype and behavioural analyses.
  • Fluorescence microscopy and image analysis

Previous Projects

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