Dr Natalia Bulgakova
Brief career history:
Using a combination of genetic assays, biochemistry and quantitative imaging techniques in Drosophila model system we study how E-cadherin functions in various developmental processes, for example cell neighbour exchange and tissue growth, and how it is regulated during development. In future, we aim to apply this knowledge about normal function of E-cadherin to treatment of medical conditions arising from defects in E-cadherin function such as epithelia-derived tumours.
PhD project opportunity
The role of posttranslational modifications in organisation and function of microtubule cytoskeleton
Funding status: Competition funded project European/UK students only
This project is eligible for a department scholarship. These scholarships are awarded on a competitive basis – find out more on our funding webpage.
Correct organization of microtubule cytoskeleton is critical for survival and function of cells in a multicellular organism. Intracellular vesicles and organelles are transported along microtubules to the to places where they are required, and in amounts needed for normal cell functions. We use a simple model organism, the fruit fly Drosophila melanogaster, to study organization and function of microtubule cytoskeleton in epithelial cells.
Recently, we discovered that the organization of microtubule cytoskeleton in epithelial cells is largely influenced by the geometric constraints of the cell. This organization is highly reproducible between cells and genotypes, and is insensitive to perturbations in microtubule dynamics, their number and interactions. We also found that in each cell there are microtubules, which are either acetylated or tyrosinated: the two most common and clinically relevant posttranslational modifications of microtubules.
On the molecular level, acetylation and tyrosination regulate stability and dynamics of microtubules and their interactions with various proteins, for example motor proteins that transport cargo along them. Therefore, these modifications are likely to affect organization and function of microtubule cytoskeleton in a cell. Their incorrect acetylation and tyrosination, however would interfere with cell functions and lead to disease or developmental defects. Indeed, modifications of acetylation and tyrosination profiles of microtubules correlate with cancer progression. However, little is known about how acetylation and tyrosination of microtubules is regulated in an organism, and what are the functions of these modifications on cell and tissue levels.
In collaboration with Dr. Juan Manuel Gomez, University of Cologne, we are currently identifying enzymes that add and remove acetyl and tyrosine groups on microtubules in flies, which will enable understanding roles of these modifications in development and disease. The aim of this project is to understand the role of acetylation and tyrosination in organization of microtubule cytoskeleton and its function using well characterized and reproducible sub-apical microtubule network in Drosophila embryonic epidermis as a model system.
The specific objectives of the project are:
1. To generate Drosophila lines for constitutive and acute inactivation of identified microtubule-modifying enzymes;
2. To determine how these modifications affect organization of microtubule cytoskeleton;
3. To discover roles of these modifications on cell and organism levels.
During the project progression, the student will receive training in a wide range of techniques including molecular biology (generation of Drosophila transgenic and mutant lines using CRISPR/Cas9), state-of-art microscopy (live imaging, super-resolution) and computational approaches.
This project is highly interdisciplinary and will be done in collaboration with Dr. Juan Manuel Gomez, University of Cologne, who will investigate the impact of these modifications in tissue morphogenesis and applied mathematicians from the group of Dr. Lyubov Chumakova, University of Edinburgh, who will develop in silico models of how posttranslational modifications affect organization and function of microtubules in a cell. Altogether, the outcomes of this project will yield fundamental knowledge about regulation of microtubule cytoskeleton, which is relevant to human biology and disease.
Keywords: Cell Biology / Development
For informal enquiries about the project or application process, please feel free to contact me:
For further information about this project and how to apply, see our PhD Opportunities page:
- Gomez JM, Chumakova L, Bulgakova NA & Brown NH (2016) Microtubule organization is determined by the shape of epithelial cells. Nature Communications, 7. View this article in WRRO
- Bulgakova NA & Brown NH (2016) Drosophila p120-catenin is crucial for endocytosis of the dynamic E-cadherin-Bazooka complex. Journal of Cell Science, 129(3), 477-482. View this article in WRRO
- Bulgakova NA, Grigoriev I, Yap AS, Akhmanova A & Brown NH (2013) Dynamic microtubules produce an asymmetric E-cadherin–Bazooka complex to maintain segment boundaries. The Journal of Cell Biology, 201(6), 887-901. View this article in WRRO