We study cellular signalling pathways in nerve cells and how these pathways contribute to neurological disorders like epilepsy and Parkinson's disease.
We are based in the Maurice Wohl Clinical Neuroscience Institute in the Department of Basic and Clinical Neuroscience at King's College London.
Our research is funded through government and charitable grants.
People
Professor of Molecular Neuroscience
Themes
Mitochondrial signalling
Mitochondria are tiny structures within cells, which play a critical role in cellular energy production and metabolism. When these 'powerhouses' malfunction, it can result in chronic illness. Mitochondrial diseases are a group of genetic disorders that cause damage to cells and tissues in the body and affect up to 1 in 4300 people in the UK. There are currently no preventative treatments for mitochondrial diseases. Extensive evidence from animal and clinical studies also suggests that defective mitochondria play a critical role in other neurodegenerative diseases, including Alzheimer's and Parkinson's disease. We are interested in how mitochondria communicate with the surrounding nerve cell, through 'mitochondrial signalling'. We and others have shown that when nerve cells are stressed or damaged, as happens in neurodegenerative disease, mitochondrial signalling pathways are activated. Excitingly, we can target these pathways to improve the function of nerves, suggesting that targeting mitochondrial signalling pathways might be a way to treat and prevent mitochondrial disease and neurodegenerative diseases such as Alzheimer's and Parkinson's disease.
mTOR signalling
mTOR, or mechanistic target of rapamycin, is a large protein kinase and a crucial sensor of cellular anabolic processes. mTOR signalling regulates a wide variety of cellular functions, including growth control, mitochondrial function, autophagy and lipid synthesis. Activation of mTOR signalling also causes neurological diseases associated with epilepsy, autism spectrum disorders and intellectual disability. We are interested in understanding the role of mTOR in nervous system development and how activation of mTOR signalling causes neurological disease. In the long term, understanding how mTOR contributes to neurological disease will lead to new treatments for these devastating diseases.
Publications
Key recent publications:
- Granat et al., 2023. Yeast NDI1 reconfigures neuronal metabolism and prevents the unfolded protein response in mitochondrial complex I deficiency. PLOS Genetics. https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1010793
- Baskaran et al., 2022. Phosphorylation of the novel mTOR substrate Unkempt regulates cellular morphogenesis. Journal of Biological Chemistry. https://www.jbc.org/article/S0021-9258(22)01231-5/fulltext
- Hunt et al., 2019. Mitochondrial stress causes neuronal dysfunction via an ATF4-dependent increase in L-2-hydroxyglutarate. Journal of Cell Biology. http://doi.org/10.1083/jcb.201904148
- Duncan et al., 2018. Ras-ERK-ETS inhibition alleviates neuronal mitochondrial dysfunction by reprogramming mitochondrial retrograde signaling. PLOS Genetics. http://doi.org/10.1371/journal.pgen.1007567
- Gatt et al., 2016. Dementia in Parkinson's disease is associated with enhanced mitochondrial complex I deficiency. Movement Disorders. http://doi.org/10.1002/mds.26513
- Cagin et al., 2015. Mitochondrial retrograde signaling regulates neuronal function. Proc Natl Acad Sci USA. http://doi.org/10.1073/pnas.1505036112
Reviews:
- Girodengo et al., 2022. Mechanistic target of rapamycin signaling in human nervous system development and disease. Frontiers in Molecular Neuroscience. https://www.frontiersin.org/articles/10.3389/fnmol.2022.1005631/full
- Granat et al., 2020, Mitochondrial retrograde signalling in neurological disease. Philosophical Transactions of the Royal Society B: Biological Sciences. https://doi.org/10.1098/rstb.2019.0415
- Bateman, 2018. Special Issue on ‘ROS and mitochondria in nervous system function and disease. FEBS Letters. https://doi.org/10.1002/1873-3468.13008
- Hunt et al., 2017. Mitochondrial retrograde signaling in the nervous system. FEBS Letters. https://doi.org/10.1002/1873-3468.12890
- Tee et al., 2016. The role of mTOR signalling in neurogenesis, insights from tuberous sclerosis complex. Seminars in Cell and Developmental Biology. https://doi.org/10.1016/j.semcdb.2016.01.040
View all publications:
Group members
- Emma Hamer (PhD student)
- Marie Girodengo (PhD student)
- Debbra Knorr (Postdoc)
- Sylvine Lalnunhlimi (mTOR Diseases Pathway node Project Manager)
- Leila Ben-Chaabane (Research Assistant)
People
Professor of Molecular Neuroscience
Themes
Mitochondrial signalling
Mitochondria are tiny structures within cells, which play a critical role in cellular energy production and metabolism. When these 'powerhouses' malfunction, it can result in chronic illness. Mitochondrial diseases are a group of genetic disorders that cause damage to cells and tissues in the body and affect up to 1 in 4300 people in the UK. There are currently no preventative treatments for mitochondrial diseases. Extensive evidence from animal and clinical studies also suggests that defective mitochondria play a critical role in other neurodegenerative diseases, including Alzheimer's and Parkinson's disease. We are interested in how mitochondria communicate with the surrounding nerve cell, through 'mitochondrial signalling'. We and others have shown that when nerve cells are stressed or damaged, as happens in neurodegenerative disease, mitochondrial signalling pathways are activated. Excitingly, we can target these pathways to improve the function of nerves, suggesting that targeting mitochondrial signalling pathways might be a way to treat and prevent mitochondrial disease and neurodegenerative diseases such as Alzheimer's and Parkinson's disease.
mTOR signalling
mTOR, or mechanistic target of rapamycin, is a large protein kinase and a crucial sensor of cellular anabolic processes. mTOR signalling regulates a wide variety of cellular functions, including growth control, mitochondrial function, autophagy and lipid synthesis. Activation of mTOR signalling also causes neurological diseases associated with epilepsy, autism spectrum disorders and intellectual disability. We are interested in understanding the role of mTOR in nervous system development and how activation of mTOR signalling causes neurological disease. In the long term, understanding how mTOR contributes to neurological disease will lead to new treatments for these devastating diseases.
Publications
Key recent publications:
- Granat et al., 2023. Yeast NDI1 reconfigures neuronal metabolism and prevents the unfolded protein response in mitochondrial complex I deficiency. PLOS Genetics. https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1010793
- Baskaran et al., 2022. Phosphorylation of the novel mTOR substrate Unkempt regulates cellular morphogenesis. Journal of Biological Chemistry. https://www.jbc.org/article/S0021-9258(22)01231-5/fulltext
- Hunt et al., 2019. Mitochondrial stress causes neuronal dysfunction via an ATF4-dependent increase in L-2-hydroxyglutarate. Journal of Cell Biology. http://doi.org/10.1083/jcb.201904148
- Duncan et al., 2018. Ras-ERK-ETS inhibition alleviates neuronal mitochondrial dysfunction by reprogramming mitochondrial retrograde signaling. PLOS Genetics. http://doi.org/10.1371/journal.pgen.1007567
- Gatt et al., 2016. Dementia in Parkinson's disease is associated with enhanced mitochondrial complex I deficiency. Movement Disorders. http://doi.org/10.1002/mds.26513
- Cagin et al., 2015. Mitochondrial retrograde signaling regulates neuronal function. Proc Natl Acad Sci USA. http://doi.org/10.1073/pnas.1505036112
Reviews:
- Girodengo et al., 2022. Mechanistic target of rapamycin signaling in human nervous system development and disease. Frontiers in Molecular Neuroscience. https://www.frontiersin.org/articles/10.3389/fnmol.2022.1005631/full
- Granat et al., 2020, Mitochondrial retrograde signalling in neurological disease. Philosophical Transactions of the Royal Society B: Biological Sciences. https://doi.org/10.1098/rstb.2019.0415
- Bateman, 2018. Special Issue on ‘ROS and mitochondria in nervous system function and disease. FEBS Letters. https://doi.org/10.1002/1873-3468.13008
- Hunt et al., 2017. Mitochondrial retrograde signaling in the nervous system. FEBS Letters. https://doi.org/10.1002/1873-3468.12890
- Tee et al., 2016. The role of mTOR signalling in neurogenesis, insights from tuberous sclerosis complex. Seminars in Cell and Developmental Biology. https://doi.org/10.1016/j.semcdb.2016.01.040
View all publications:
Group members
- Emma Hamer (PhD student)
- Marie Girodengo (PhD student)
- Debbra Knorr (Postdoc)
- Sylvine Lalnunhlimi (mTOR Diseases Pathway node Project Manager)
- Leila Ben-Chaabane (Research Assistant)
Contact us
Joseph Bateman
Maurice Wohl Clinical Neuroscience Institute
Department of Basic and Clinical Neuroscience
King’s College London
5 Cutcombe Road
London
SE5 9RX
UK