PhD Projects

We are currently looking for enthusiastic students interested in joining the lab to pursue their PhD (see below for exciting potential projects and funding schemes). Interested candidates should get in contact with Dr. Dhanya Cheerambathur.

Projects for students

Project I – How do microtubule regulators facilitate neuronal circuit formation?

The aim of this project is to understand how the microtubule cytoskeletal machinery facilitates neuronal morphogenesis and the proper wiring of the nervous system.

The central nervous system is a complex network of neurons and supporting cells that form the information relaying unit of an organism. The assembly of this network is a highly orchestrated event that involves neurite outgrowth, fasciculation, and synapse formation to generate a functional nervous system. How these organizational features emerge during development is poorly understood. Microtubules are critical for neuron formation and function. These long protein polymers are dynamic structural elements within the neuron. As neurons develop, microtubules are organized and sculpted by the cell machinery to form the axons, dendrites, and neural network. Despite the central role of the microtubule, little is known about how the microtubule cytoskeleton contributes to the assembly of the neural circuit.

Recently, work from us and others has uncovered a cell division-independent function for the kinetochore proteins in shaping the nervous system. Kinetochores are multiprotein structures that assemble on the centromeric DNA to connect chromosomes with spindle microtubules during mitosis. We discovered that the core microtubule binding machinery within the kinetochore, the 10-subunit KMN network (KMN: Knl1-complex/Mis12-complex/Ndc80-complex), is redeployed post-mitotically to pattern the sensory nervous system in C. elegans. Specifically, post-mitotic degradation of KMN proteins from amphid sensory neurons resulted in a disorganized nerve ring, impaired dendrites and axons, and fasciculation defects.

What is the function of the kinetochore microtubule machinery in a developing neuron? This project will focus on understanding this novel post-mitotic neuronal function of kinetochores in C. elegans and mammalian cell culture systems.

For more information:

https://www.findaphd.com/phds/project/how-do-microtubule-regulators-facilitate-neuronal-circuit-formation/?p125739

Several sources of funding are available, get in contact with Dr. Dhanya Cheerambathur to discuss the options.


Project II – Building a temporal proteomics map of the developing C. elegans nervous system

This interdisciplinary project is part of the Wellcome Four Year PhD Programme in Integrative Cell Mechanisms and combines our expertise in studying neuro-developmental mechanisms and Kustatscher Lab expertise in developing novel quantitative tools to study dynamic changes in cellular proteomes.

The development of the nervous system is a complex process, producing a tissue highly specialized in intra- and intercellular information transfer. Central to neurodevelopment is the transformation of a neuronal precursor into a highly asymmetrically shaped neuron with unique signaling structures (e.g., axon, dendrite and synapse). The formation of these structures is a multistage, well-orchestrated process associated with significant remodeling of the neuronal proteome. Although a number of neuron-specific factors have been identified, the precise proteomic alterations that facilitate neuronal morphogenesis during organismal development are poorly understood. This project aims to build a quantitative proteomic profile of neuronal morphogenesis and identify key factors underpinning neuronal structural changes.

For more information:

https://www.wcb.ed.ac.uk/iCMPhD


Project for EASTBIO studentship

This is a collaborative project between our lab and the lab of Dr. Tony Ly at the School of Life Sciences in Dundee. This project is open to students from all nationalities .

Project III – Investigating the role of microtubule cytoskeleton in building the neuronal connectome

This project will focus on how the microtubule cytoskeleton function within the pioneer neurons to facilitate the assembly of neural circuits.

During neural development, pioneer neurons extend axons in response to guidance cues from other neurons and non-neuronal cells to establish the framework that build the neural circuits. The assembly of this circuit is a highly orchestrated event that initiates with the pioneer axon outgrowth which is followed by fasciculation (axon bundling) and synapse formation with the axons of follower neurons. How these organizational features emerge during development is poorly understood.

Microtubules, polymers of alpha and beta-tubulin are critical to the structure and function of all types of neurons. Several microtubule related proteins are linked to mutations that underlie neurological and brain development disorders. Despite the central role of the microtubule in the neurons, little is known about the identity and function of microtubule cytoskeleton in specific neuronal subtypes such as the pioneer neurons. To tackle this problem, the project will draw on the expertise of the Cheerambathur-lab expertise in studying neurodevelopmental mechanisms using C. elegans and Ly-lab expertise in developing novel quantitative tools to study dynamic changes in cellular proteomes.

For more information:

https://www.findaphd.com/phds/project/eastbio-investigating-the-role-of-cell-polarity-pathways-during-neurite-formation/?p113443