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  Multiplex imaging to uncover key biomarkers and whole brain neuron circuit interaction during stroke recovery.


   School of Electrical Engineering, Electronics and Computer Science

  , Dr Li-An Chu  Wednesday, July 31, 2024  Competition Funded PhD Project (Students Worldwide)

About the Project

We aim to comprehensively depict the activity patterns of the mouse brain in recovering from ischemic stroke through the development of a series of new technologies from various teams. By establishing this analyzing how the brain's neural function is reconstructed during physical rehabilitation or chemical therapy, the project aims to provide new therapeutic opportunities for human stroke treatment in the future.

Through the analysis of multiplex biomarker chips and whole-brain multicolor microscopy imaging in a mouse stroke model, we can gain in-depth insights into the pathological mechanisms of global neuronal damage caused by stroke and the interactive effects among different neurons during the recovery process of brain tissue damage. This approach allows the assessment of various recovery strategies, including physical therapy, drug treatment, and combined therapies, on post-stroke recovery outcomes and their impact on the neural circuits in the brain. These research findings can guide clinical practice in determining the most effective recovery methods. By studying biomarkers and neuroplasticity and recovery mechanisms in mice after a stroke, we can gain a deeper understanding of how the brain undergoes restructuring and repair. This knowledge is crucial for developing therapeutic approaches that promote neural regeneration and recovery.

To develop new methodologies and technologies to enhance the detection, monitoring and understanding of bio markers linked to stroke occurrence and recovery. Two distinct approaches and technologies will be investigated and then combined to achieve this aim:

-       Development of low cost point of care blood tests to monitor the the levels of known bio-markers associated with stroke. This work will be lead by UoL and involve the development of an “External Gate Field Effect Transistor (EG-FET)”, where the external gate is functionalized with aptamers capable of specific binding to these known bio-markers. If the target bio-markers are then present in the specimen sample they will bind to the gate electrode, which in turn will produce a mirror charge on the gate of the FET and create a measurable change in the current. Devices will first be developed and calibrated using markers dispersed in buffer solutions, before then being used with real samples.

-       Development of enhanced microscope and imaging systems for the detection and monitoring of relevant bio-markers. Current known bio markers associated with stroke and stroke recovery include C-reactive protein (CRP), interleukin-6 (IL-6), as well as neurotrophic factors like brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF). All of these have known aptamer sequences available to use with an EG-FET system.

By utilising these two distinct, yet complementary techniques several further advancements and modificaions will also be investigated, including.

-       Investigating the potential use of aptamers to enhance the quality / performance of imaging systems. This could be by either utilizing aptamers to help capture and imombilise the bio markers, including with potential steps to amplify their signal(s). An alternative approach could be to use fluorescently labelled aptamers to help identify the presence of bio markers.

-       Combining the data and information from both the aptamer based sensor and the imaging approaches to potentially identify new bio markers or help inform discussion on the hirecacy of imporatnace between different bio markers.

To develop new methodologies and technologies to monitoring and understanding how whole brain neuron regeneration during stroke recovery, the following two approaches will be taken:

-       Establishment of Deformation-Free Whole-Brain Multicolor Staining Method in Mice:We aim to develop a tissue processing method that enhances sample robustness. This method combines an organic solvent and a water-soluble delipidation process. It meets the requirements of delipidation and repeated immunostaining without using electrophoresis, thus avoiding tissue damage caused by electrophoresis and sample deformation resulting from multiple staining sessions.

-       Reconstruction and Analysis of Neuronal Images of the Whole Mouse Brain: We aim to fully develop and implement a deep learning model for neuronal and cellular segmentation in samples with high-contrast variability and intensity variations. Simultaneously, we will use cFOS expression co-localize with various types of cells that express different neuron transmitters to confirm the types and distribution of neuroactive substances in different periods and across the entire brain.

We want all of our staff and Students to feel that Liverpool is an inclusive and welcoming environment that actively celebrates and encourages diversity. We are committed to working with students to make all reasonable project adaptations including supporting those with caring responsibilities, disabilities or other personal circumstances. For example, If you have a disability you may be entitled to a Disabled Students Allowance on top of your studentship to help cover the costs of any additional support that a person studying for a doctorate might need as a result.

We believe everyone deserves an excellent education and encourage students from all backgrounds and personal circumstances to apply.

 

Applicant Eligibility

Candidates will have, or be due to obtain, a Master’s Degree or equivalent from a reputable University in an appropriate field of Engineering. Exceptional candidates with a First Class Bachelor’s Degree in an appropriate field will also be considered.

 

Application Process

Candidates wishing to apply should complete the University of Liverpool application form [How to apply for a PhD - University of Liverpool] applying for a PhD in **Aerospace / Civil / Materials / Mechanical** Engineering and uploading: Degree Certificates & Transcripts, an up-to-date CV, a covering letter/personal statement and two academic references. 


Biological Sciences (4) Computer Science (8) Engineering (12) Medicine (26)

Funding Notes

This funded studentship will cover tuition fees and pay a maintence grant similar to a UKRI studentship (£18,622/year) for 2 years at while in Liverpool and 15233 NDT/month while in Taiwan for 2 years. The studentship also come with additional financial support of a research training support grant which will fund the cost of materials, conference attendance etc.


References

https://doi.org/10.7554/eLife.93212.4

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