Research Projects
Here is a selection of ongoing Research Projects:
Gene therapy for drug resistant epilepsy
Around 30% of people with epilepsy do not respond adequately to anti-epileptic drugs. Non-pharmaceutical therapeutic approaches based on gene therapy are emerging. We are exploring two gene therapy strategies; increasing the ability of astrocytes to buffer extracellular potassium and glutamate; and targeting homeostatic regulators of neuronal excitability.
Key Collaborators
Prof Nicolas Mazarakis, Imperial College London, Prof Richard Baines & Prof Stuart Allan Universality of Manchester.
Funding
RosetreesTrust, Research England, MRC IAA, MRC TAS
Investigating the impact of seizure-associated spreading depolarisations in epilepsy
Spreading depolarisations (SDs) and seizures can co-exist and there are complex spatiotemporal interactions between the two phenomena. The events leading to SD initiation in epileptic tissue remain poorly characterised. To investigate this, we employ DC-Coupled video-telemetry or bilateral widefield calcium imaging concurrent with graphene micro-transistor recordings in awake head-fixed mice using a variety of acute seizure and chronic epilepsy models. Using this methodology combined with measurements of autonomic function we are evaluating the impact of seizure-associated SDs to the pathophysiology of epilepsy.
Key Collaborators
Prof Kiril Volynski, Prof Beate Diehl, Prof Dmitri Rusakov, UCL Institute of Neurology. Dr Anton Guimerà-Brunet, CNM-CISC.
Funding
European Union Graphene Flagship, Epilepsy Research UK & Medical Research Council (MRC).
Determining the influence of seizures and spreading depolarisation to tumour growth in glioblastoma.
Glioblastoma multiforme/glioblastoma (GBM) is a grade IV primary malignant glioma with a median survival time of only 15 months. A direct link between peri-tumoural excitability and tumour progression exists, with brain hyper-excitability increasing the rate at which tumour cells proliferate. Seizures are a pathophysiological feature of glioblastoma (GBM) and are an increasingly validated biomarker for disease progression or recurrence. We use video-telemetry and graphene micro-transistor arrays to characterise the spatial and temporal occurrence of seizures and spreading depolarisation in preclinical models of glioblastoma-related epilepsy. We are developing strategies to reduce peri-tumoural excitability to determine whether this results in delayed tumour growth and increased survival duration.
Key Collaborators
Prof Kostas Kostarelos & Dr Thomas Kisby, University of Manchester. Dr Anton Guimerà-Brunet, CNM-CISC.
Funding
Manchester University NOWNANO PhD Programme. European Union Graphene Flagship
The impact of Spreading depolarisation on cerebral blood flow in the post-stroke brain
Immediately after a stroke there can be early seizures and spreading depolarisations lasting a few hours to days. It is thought that the frequency and duration of SDs in particular play a significant role in infarct size. SDs can induce hypoperfusion in at-risk tissue surrounding the ischaemic core. Graphene micro-transistor arrays allow detection of SDs without the signal attenuation, distortion or voltage drift associated with traditional metal-based electrodes. Additionally, they are transparent and compatible with several imaging modalities including functional ultrasound and laser speckle contrast imaging of blood flow. We are applying these techniques to map SD and haemodynamic responses in the post-stroke brain and evaluating therapeutic approaches that target SDs to determine whether they result in reduced stroke severity.
Key Collaborators
Prof Stuart Allan, Prof Kostas Kostarelos University of Manchester, Dr Anton Guimerà-Brunet, CNM-CISC.
Funding
European Union Graphene Flagship & Medical Research Council UK
Brain Stimulation Therapy
​Graphene microelectrodes can be made highly porous increasing the electrochemical surface area. They have low impedance, extremely high charge injection limit, and outstanding stability, making them suitable for brain stimulation. We are working with our collaborators within the Graphene Flagship (ICN2, INBRAIN Neuroelectronics) to develop graphene stimulating electrodes useful for closed-loop cortical stimulation in neocortical epilepsy and in neurological diseases that may benefit from deep brain stimulation therapy including temporal lobe epilepsy and Parkinson’s disease.
Key Collaborators
Funding
Prof Kostas Kostarelos University of Manchester, Dr Anton Guimerà-Brunet, CNM-CISC, Prof Jose Garrido ICN2.
European Union Graphene Flagship & UKRI Close-NIT (MRC/EPSRC)
Developing the MRI compatibility of graphene micro-transistor arrays
It is highly desirable to allow visualisationof the brain using MRI in the vicinity of invasive probes. However, metal-based electrodes cast a large artifact obscuring tissue directly adjacent to the recording sites. Graphene micro-transistors are essentially invisible under MR. Using strategically placed fiducial markers we are designing transistor depth probes that are MRI compatible to enable high spatial resolution localisation and multi-modal concurrent acquisitions, e.g. EEG-fMRI.
Key Collaborators
Prof Louis Lemieux UCL Institute of Neurology, Dr Ben Dickie, Prof Kostas Kostarelos University of Manchester, Dr Anton Guimerà-Brunet, CNM-CISC.
Funding
Engineering & Physical Sciences Research Council.
