Mitochondria in development: Neural stem cell-niche interactions that protect the developing and aging brain against mitochondrial dysfunction
Mitochondrial diseases are genetic disorders that impair the energy production in our cells and affect about 1 in 5,000 people in the UK. Production of energy is crucial for normal functioning of all cells and organisms. Nevertheless, symptoms of mitochondrial disease can be very diverse and tissue-specific and often only appear in adult life. This suggests that some tissues and stages of life are relatively protected from mitochondrial dysfunction, while others are more susceptible.
In the lab, we study how cells and tissues respond to mitochondrial dysfunction. The brain is the main focus of our research as it is frequently affected by mitochondrial disease, with a major impact on disability and death. Our overall aim is to identify novel determinants of tissue-specific phenotypes of mitochondrial and neurodegenerative diseases, and to uncover potential therapeutic targets to treat these disorders.
The main research themes are (1) how cell-type composition of a tissue and cell-to-cell communication may provide protection against mitochondrial disease, and (2) how transcription of the nuclear genome is regulated when a cell is confronted with mitochondrial dysfunction.
We use a wide range of approaches, but our favourite model system is the fruit fly, Drosophila melanogaster. Up to 70% of all human disease genes also have orthologs in Drosophila, and thanks to its powerful genetics, Drosophila is widely used as a model to study development and human disease. We employ advanced genetic tools and combine these with confocal and super-resolution imaging, biosensors, and innovative DamID-based sequencing approaches to study the autonomous and non-cell-autonomous effects of tissue- and cell-type specific mitochondrial dysfunction in vivo, in the developing and aging brain.
Ultimately, we hope to uncover potential therapeutic targets to treat mitochondrial and neurodegenerative disorders. This will provide novel insight for other conditions where mitochondrial dysfunction plays a role too, including diabetes and cancer.
Biography
As a medical student at Ghent University (Belgium), Jelle became interested in developmental neurobiology and joined Pierre Vanderhaeghen's lab at the ULB in Brussels to study transcriptional regulation of brain development. His PhD (2014) and neurology training sparked an interest in mitochondrial genetics and metabolism. Thanks to postdoctoral fellowships from EMBO and Wellcome (2014-2019), he then moved to the lab of Andrea Brand at the Gurdon Institute in Cambridge to study metabolism of brain development in Drosophila, and to develop innovative DamID-based approaches for genome-wide chromatin profiling in Drosophila and vertebrates. He joined the Department of Clinical Neurosciences and the MBU in Cambridge in 2020 funded by a Clinical Research Career Development Fellowship from Wellcome.
At the MBU, Jelle chairs the MBU WIDE (Wellbeing, Inclusion, Diversity and Equality) group. As a positive culture champion at the School of Clinical Medicine and as part of the Mid-Career Fellows (MCF) Network, he tries to promote a culture of integrity, openness and enthusiasm within and outside the lab and aims to enhance environmental sustainability wherever possible.
As a neurologist, Jelle continues to do clinical work and actively participates in the clinical research programme MitoCamb of the mitochondrial genetics clinic in Addenbrooke’s, together with Patrick Chinnery and Rita Horvath.
Publications
Selected Publications
[11C]PK11195-PET brain imaging of the mitochondrial translocator protein in mitochondrial disease.
Neurology 96(22), e2761-e2773
