PhD Quantitative analysis of behavioural recovery after brain injury in larval zebrafish through computational modelling

Closing Date

5 Dec 2018

Address

College of Medicine and Veterinary Medicine, University of Edinburgh

Project Description

A PhD project is available in the research group of Dr Leah Herrgen (Centre for Discovery Brain Sciences, University of Edinburgh) in collaboration with Dr Arno Onken (School of Informatics, University of Edinburgh). The successful candidate will work on an exciting interdisciplinary project at the crossroads of neuroscience, tissue repair and computational biology. 

Neuronal injury disrupts the structure and function of the brain’s intricate neural circuits, and thereby endangers the health and viability of the affected individual. In contrast to humans, lower vertebrates such as fish and frogs have the capacity to recover from brain injury, but the underlying mechanisms are not understood. Previous work from the Herrgen group has demonstrated an important role for calcium-mediated tissue contractions in creating an environment conducive to repair [1]. Ongoing research focusses on how neuronal structure and function change during injury and repair in the optic tectum of larval zebrafish. An essential next step will be to investigate how tectal injury affects visually guided behaviours (e.g. prey capture, predator avoidance), and to integrate this with our results on injury-induced changes in neuronal structure and function. 

To achieve this, the student will first establish behavioural assays for quantitative analysis of visually guided behaviours in larval zebrafish. This will involve the construction of an experimental setup for acquisition of behavioural data through in vivo imaging; and the development of algorithms for quantification and classification of different behavioural patterns through analysis of the kinematic properties of tail movements. In this the student will be supervised by Dr Arno Onken, an expert in the development of flexible probabilistic models and machine learning methods and their application to complex biological data [2]. The student will then use these behavioural assays to obtain information on the time course of behavioural recovery after brain injury. Furthermore, s/he will use genetic and pharmacological manipulations of candidate signalling pathways involved in structural repair (e.g. Rho GTPases) and functional recovery (e.g. NMDA receptors) to investigate the molecular mechanisms underlying behavioural recovery. 

The interdisciplinary nature of the project will allow the successful candidate to acquire a wide range of knowledge and skills in neuroscience, tissue repair and computational biology. The Herrgen lab will provide training in zebrafish breeding and micromanipulation, molecular biology, in vivo imaging, and behavioural assay setup and validation. Training in advanced data analysis and quantification, in particular unsupervised machine learning algorithms for feature extraction as well as supervised algorithms for behavioural classification, will be conducted in the lab of Dr Arno Onken. This will include both conceptual training in the methodological aspects of the project and support to ensure that the student develops the skills necessary to carry out the computational analysis (e.g. familiarity with Python programming and the Python Data Science Stack). 

The ideal candidate should have a genuine interest in quantitative cellular and systems neuroscience. Previous experience with zebrafish and behavioural assays and the ability to write code would be desirable but are not strictly required. Preliminary enquiries about the project are encouraged and should be directed to Leah.Herrgen@ed.ac.uk. 

Applications: 
Completed application form along with your curriculum vitae should be sent to our PGR student team at RDSVS.PGR.Admin@ed.ac.uk 

References: 
Please send the reference request form to two referees. Completed forms for University of Edinburgh College of Medicine and Veterinary Medicine project should be returned to RDSVS.PGR.Admin@ed.ac.uk by the closing date: 5th December 2018. 

It is your responsibility to ensure that references are provided by the specified deadline. 

Download application and reference forms via: 
https://www.ed.ac.uk/roslin/postgraduate/bbsrc-eastbio-dtp 

Funding Notes

Eligibility: 
All candidates should have or expect to have a minimum of an appropriate upper 2nd class degree. To qualify for full funding students must be UK or EU citizens who have been resident in the UK for 3 years prior to commencement. 

References

[1] Herrgen L, Voss OP, Akerman CJ. Calcium-dependent neuroepithelial contractions expel damaged cells from the developing brain. Dev Cell 2014;31:599–613. 
[2] Onken A, Liu JK, Karunasekara PPCR, Delis I, Gollisch T, Panzeri S. Using matrix and tensor factorizations for the single-trial analysis of population spike trains. PLoS Comp Biol 2016; 12(11): e1005189. 

Contact Details

Leah.Herrgen@ed.ac.uk
RDSVS.PGR.Admin@ed.ac.uk