Advanced imaging and mathematical modelling of ageing and neurodegeneration in the nervous system
Lead Research Organisation:
University of Manchester
Department Name: School of Biological Sciences
Abstract
This project is highly interdisciplinary at the cross-roads of mathematical modelling and cell-/neurobiological research involving advanced live imaging, electron microscopy (EM), tomography and genetics. It will investigate processes of ageing and degeneration in the nervous system, focussing on mechanisms underpinning the longevity of axons. Axons are the cable-like (~1mm in diameter, metres-long) extensions of neurons which wire the nervous system. These delicate structures are maintained for many decades in humans. They are key lesion sites in spinal cord injury, trauma and many neurodegenerative diseases (e.g. spastic paraplegia), and we lose 50% of our axons during healthy ageing. The essential structural backbone of axons is formed by continuous bundles of filamentous protein-polymers called microtubules. Disorganisation of these microtubule bundles leads to axon swellings correlating with axon decay, but the underlying mechanisms preventing/causing disorganisation are not at all understood. To gain this understanding, work on this project will use genetically induced MT disorganisation in combination with advanced imaging to capture volume and space relationships (EM) as well as the dynamics of MT disorganisation processes (live imaging). Based on the collected data and existing algorithms for MTs, computational/mathematical models describing MT disorganisation will be developed and the underlying rules deduced.
Literature:
axons: Prokop, 2013, Neur Dev 8, 17ff.
genetics: Prokop, 2013, J Cell Sci. 126, 2331ff.
mathematics: Ziebert, 2015, Phys Rev Lett 114, 148101ff.
live imaging: Alves-Silva, 2012, J Neurosci 32, 9143ff.
EM: Starborg, 2013, Nat Protoc 8, 1433ff.
Literature:
axons: Prokop, 2013, Neur Dev 8, 17ff.
genetics: Prokop, 2013, J Cell Sci. 126, 2331ff.
mathematics: Ziebert, 2015, Phys Rev Lett 114, 148101ff.
live imaging: Alves-Silva, 2012, J Neurosci 32, 9143ff.
EM: Starborg, 2013, Nat Protoc 8, 1433ff.
Organisations
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| BB/M011208/1 | 01/10/2015 | 31/03/2024 | |||
| 1791002 | Studentship | BB/M011208/1 | 01/10/2016 | 31/03/2021 |
| Description | I want to understand how curled MT disorganisations form. For this, I compare patterns of microtubule disorganisation under different pathological conditions, specifically their degrees of curvature versus straightness. However, assessing curvature is not trivial, and all current methods pose problems. To overcome the various disadvantages, our new approach uses Hough transform aligned with graph theory as a quick and reliable way to find straight lines. To assess curvature, we combine improved Gaussian filters with Fourier transforms, thus combining the advantages of both methods. These combined algorithms were implemented computationally, and I developed the user-friendly MATLAB application ALFRED (Advanced Labelling, Fitting, Recognition and Enhancement of Data), able to import many image formats, skeletonise these images and apply our new analysis strategies. The publication is in preparation, its application for our purposes is underway. |
| Exploitation Route | On a number of conferences about 10 groups have expressed their interest to collaborate. |
| Sectors | Digital/Communication/Information Technologies (including Software) |
| Title | Straightness and curvature analysis |
| Description | I've developed a software (described in the software section) that initially was meant for neuronal image analysis but has evolved into a more general one, with a major focus on analysing not only straight segments (using graph theory and a Hough transform) but also the curvature (using Fourier fitting and Gaussian filters), which is a complicated problem described in the literature. The parameters can then be used to inform mathematical models. |
| Type Of Material | Computer model/algorithm |
| Year Produced | 2019 |
| Provided To Others? | No |
| Impact | There aren't many results yet as the software only now has gotten to a point where it's usable, but from conferences and other meetings, I've had a lot of people interested in collaborating and, as such, we predict that it will have a reach beyond our own research interests. |
| Title | ALFRED: Advanced Labelling, Fitting, Recognition and Enhancement of Data |
| Description | The software implements the methods described in the Data analysis/models section, but it's a general public accessible software that can analyse any type of images where the main focus is the understanding of straightness and curvature of the images. It is developed to a point where there is as little user input as possible to allow a more user-independent and objective analysis of the images. |
| Type Of Technology | Software |
| Year Produced | 2019 |
| Impact | There aren't any notable impacts yet as the software only now reached a stage where it can be fully used by others, but from conferences and other research meetings, there's a lot of interest in potential collaborations or free use of the software, which makes us believe that it will be used far beyond our research interests. |
| Description | Christmas Markets Workshop at Kings Cross |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | It was a workshop to explain artificial intelligence to the wider audience, and Beatriz coordinated and organised the event. It was for two hours at the Canopy Christmas Markets and over 100 people, from kids to seniors, showed up, participated and asked questions. |
| Year(s) Of Engagement Activity | 2019 |