UK Parkinson's Disease Consortium - UKPDC
- Principal Investigators
- Research Groups
- Cell Physiology
- Clinical Neuroscience
- Clinical Studies
- Drosophila Genetics
- Molecular Biology and Biochemistry
- Molecular Neuropathology
- Neurological Biochemistry
- Neurological Signalling
- Protein Phosphorylation
- Contact us
Public lecture: The autophagy signaling network, c-‐myc and pathology: don't mess with the cell cycle!
You are invited to a public lecture by Francesco Cecconi, an eminent scientist in the field of autophagy and neurodegeneration, on Thursday the 25th of April at 17:00, in the lecture theatre of 33 Queen Square, University College Hospital London, WC1N. The lecture will be followed by a general discussion with drinks and food. More...
Have you ever wondered how scientists research the brain? Have you wondered who digs through that beautiful mass of grey matter between our ears to understand how it works and why it stops working? Meet the Neurodegenerative Diseases Initiative. Funded by the Wellcome Trust and MRC, this team of scientists from around the globe investigates Alzheimer's, Parkinson's and Motor Neuron Diseases. The team is on the hunt for understanding and treatments for brain diseases. More...
The "Degenerating Brains" public symposium was held on the 13th March 2013, as part of Brain Awareness Week. Around 250 people showed up to hear Professors John Hardy (UCL), Chris Shaw (KCL) and David Rubinsztein (Cambridge) discuss new discoveries in neurodegenerative diseases and how they might impact drug treatment. More...
New research, published in Neuron, gives insight into how single mutations in the VCP gene cause a range of neurological conditions including a form of dementia called Inclusion Body Myopathy, Paget’s Disease of the Bone and Frontotemporal Dementia (IBMPFD), and the motor neuron disease Amyotrophic Lateral Sclerosis (ALS). More...
You are invited to an evening (13th March 2013) exploring the very latest in cutting edge research into neurodegenerative diseases. Supported by the Wellcome Trust, scientists investigating Alzheimer's, Parkinson's and Motor Neuron disease will explain how our understanding of these disorders is changing in the light of new discoveries in genetics and cell biology, and how these discoveries impact on developing new drugs for these diseases.
18.00 Welcome and introduction
18.10 Lectures commence
Cell Physiology Group
We are fascinated by the intimate dialogue between mitochondrial biology and cell signaling systems. How do cell signaling pathways impact on and regulate mitochondrial physiology? How do subtle changes in mitochondrial function affect the physiology of the cell? How are mitochondria in different cell types specialized to match the specialized differentiated function of the cells they inhabit? We are especially concerned to characterise the contributions of mitochondrial dysfunction to cell injury and cell death - by necrosis or apoptosis – that takes place in situations such as ischaemia, reperfusion injury and in the neurotoxicity mediated by glutamate or beta-amyloid. Another core theme again involving a complex dialogue is the mitochondrion as both a site and a target of oxidative stress and damage in disease models.
Most of our work involves live cell fluorescence microscopy and imaging, including confocal, multiphoton and fast read-out cooled CCD instruments. All approaches have been adapted to allow the simultaneous or near simultaneous measurement of multiple variables - cytosolic calcium and mitochondrial potential, cytosolic calcium and mitochondrial calcium, NADH autofluorescence and cytosolic calcium or cytosolic magnesium and so on. We have a broad general interest in functional cellular imaging and in the development of new approaches to imaging aspects of cell function using targeted probes, GFP tagged proteins, FRET, FLIM and so on.
Interests of the lab extend through a wide range of biological problems in which mitochondria are involved - in ischaemia reperfusion injury in the heart, in the role of mitochondrial function in fertility in the mammalian egg (with John Carroll), in mitochondrial function and septic shock syndrome in liver, kidney and muscle, in mitochondrial biogenesis following exercise and training in muscle, and in mitochondrial dysfunction in beta cells in diabetes. This rather unusual breadth has had a positive influence on all our work, as resolving problems in one system invariably seems to illuminate problems with others. We have been astonished at the frequency with which a small number of basic principles are recapitulated in a wide and disparate array of models.
There is mounting evidence that PD involves mitochondrial dysfunction, both a bioenergetic deficit especially affecting complex I and a defect in quality control, with defects in autophagy. We are interested to understand the links between these, the possible roles of mitochondrial biogenesis as a protective strategy. We are also interested in the possible roles of lysosomes as a part of the autophagic machinery, as there are strong associations between lysosomal storage diseases and PD. This latter project involves collaborations with Sandip Patel and Tony Schapira (RFH).
In this movie, mitochondrial membrane potential was measured in a field of living astrocytes in culture using confocal microscopy. Cells were loaded with rhodamine 123 and potential measured as dequench (an increase in signal means mitochondrial depolarisation). Amyloid β 1-42 was applied shortly after the start of the time series. After a delay, we see a gradual progressive depolarisation of mitochondria on which are superimposed large transient depolarisations that may recover completely.
Page last modified on 27 jan 11 15:09