Jelle van den Ameele

Jelle van den Ameele

Wellcome Clinical Research Career Development Fellow

Molecular mechanisms of tissue specificity in mitochondrial disease

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.

Publication profile - Google Scholar

Publication profile - PubMed

Research areas

Publications

Publication profile - Google Scholar

Publication profile - PubMed

Selected Publications

van den Ameele J, Fuge J, Pitceathly RDS, Berry S, McIntyre Z, Hanna MG, Lee M & Chinnery PF (2020) Chronic pain is common in mitochondrial disease. Neuromuscul Disord

van den Ameele J, Li AYZ, Ma H & Chinnery PF (2019) Mitochondrial heteroplasmy beyond the oocyte bottleneck. Semin Cell Dev Biol 97, 156 - 166

van den Ameele J & Brand AH (2019) Neural stem cell temporal patterning and brain tumour growth rely on oxidative phosphorylation. eLife 8

Tiberi L, van den Ameele J, Dimidschstein J, Piccirilli J, Gall D, Herpoel A, Bilheu A, Bonnefont J, Iacovino M, Kyba M, Bouschet T & Vanderhaeghen P (2012) BCL6 controls neurogenesis through Sirt1-dependent epigenetic repression of selective Notch targets. Nature Neuroscience 15, 1627 - 1635

Gaspard N, Bouschet T, Hourez R, Dimidschstein J, Naeije G, van den Ameele J, Espuny-Camacho I, Herpoel A, Passante L, Schiffmann SN, Gaillard A & Vanderhaeghen P (2008) An intrinsic mechanism of corticogenesis from embryonic stem cells. Nature 455, 351-7

Biography

As a medical student in Ghent (Belgium), I became interested in developmental neurobiology and joined Pierre Vanderhaeghen's lab in Brussels. There, I contributed to the first description of embryonic stem cell (ESC)-derived corticogenesis (Gaspard et al., Nature, 2008), and later employed this ESC-based system to discover a new role for the oncogene Bcl6 in cortical neurogenesis (Tiberi and van den Ameele et al., Nat Neurosci, 2012). My PhD and neurology training sparked an interest in mitochondrial genetics and metabolism, and I moved to the lab of Andrea Brand at the Gurdon Institute in Cambridge to study metabolism of brain development in vivo, in Drosophila. Funded by an EMBO long-term fellowship (2014), and a Wellcome Trust Postdoctoral Fellowship for Clinicians (2015), I identified a role for mitochondrial metabolism in Drosophila neural stem cell patterning (van den Ameele and Brand, eLife, 2019) and adapted technology for genome-wide chromatin profiling from Drosophila to mouse (Cheetham et al., Development, 2019; van den Ameele et al., in preparation).

I joined the Department of Clinical Neurosciences and the Mitochondrial Biology Unit in Cambridge in 2020 funded by a Clinical Research Career Development Fellowship from Wellcome.

I am fascinated by many aspects of molecular and developmental biology, but focus on questions relevant for understanding mitochondrial disease. I love sharing my passion for research with people in- and outside the lab, thoroughly enjoy talking about intriguing data and new technology, and look forward to applications from enthusiastic students and post-docs to join the lab. As an active member of the Equality Working Group at the Gurdon Institute during my postdoc, and father of three young children, I very much value equality and diversity. In the lab we promote a culture of integrity, openness and enthusiasm and try to enhance environmental sustainability wherever possible.

Although I spend most of my time on basic research, I continue to do clinical work and actively participate in the clinical research programme of the mitochondrial genetics clinic in Addenbrooke’s together with Patrick Chinnery and Rita Horvath.

Education

2000 - 2007
Medicine, Ghent University, Belgium
2007 - 2014
Specialty training in Neurology, Ghent University and Sint-Augustinus Hospital, Antwerp, Belgium
2009 - 2013
PhD in Medical Sciences, Pierre Vanderhaeghen Lab, Free University of Brussels, Belgium

Professional Career

2020 - present
Group Leader, Department of Clinical Neurosciences and MRC Mitochondrial Biology Unit, Cambridge
2014 - present
Honorary Consultant in Neurology, Addenbrooke’s Hospital, Cambridge
2015 – 2019
Wellcome Trust Postdoctoral Training Fellowship for Clinicians
2014 – 2015
EMBO Long-term Post-doctoral Fellow, Andrea Brand lab, Gurdon Institute, University of Cambridge