Ventura research group: Mitochondrial adaptive responses in environmentally induced neuronal aging

Liaison-Group of the IUF and the Central Institute of Clinical Chemistry and Laboratory Medicine of the Heinrich Heine University

Head of research group:
Dr. med. Dr. rer. nat. Natascia Ventura tl_files/bilder/mail.gif
(Heinrich Heine University Düsseldorf)
Telefon: 0211-3389-203

Postdocs:
Dr. Silvia Maglioni tl_files/bilder/mail.gif
Dr. Alessandra Runci tl_files/bilder/mail.gif
Dr. Alfonso Schiavi tl_files/bilder/mail.gif
Dr. Anjumara Shaik tl_files/bilder/mail.gif

PhD students:

Vanessa Brinkmann tl_files/bilder/mail.gif
Shiling Feng tl_files/bilder/mail.gif

Master student:

Christiane Seibel tl_files/bilder/mail.gif

Research profile

Environmental factors heavily impact on human health and behaviors. Mitochondria are key modulators of cellular homeostasis and may represent central hubs in response to different types of environmental and nutritional interventions. Through state-of-the-art approaches our lab exploits the nematode Caenorhabditis elegans to unravel molecular mechanisms of mitochondrial adaptation to extrinsic interventions (e.g. food components, hypoxia, pollution related particles) in modulating age- and disease-associated neurodegenerative processes, with the ultimate goal of extending healthy lifespan. To this end, we recently also developed a high-content phenotype-based screening strategy to identify compounds acting through mitochondria to protect against age- and disease-associated neurodegeneration.

Projects

1. Mechanistic aspects of mitochondrial-stress control of longevity

Through complementary genetic, biochemical and molecular approaches we investigate intracellular players affected by mitochondrial-targeting genetic and pharmacological interventions to promoting healthy aging. Targeted (autophagy, apoptosis, neuronal specific pathways) as well as unbiased strategies are concurrently used in this project funded by the Competitive Research Funding of the Medical Faculty of the Heinrich Heine University and by the DFG. Long-standing collaborations with Profs Nektarios Tavernaraki, Bart Braeckman and Hilde Nilsen are nicely contributing to this project.

2. Environmental interventions acting through mitochondria to modulate health and lifespan

In this DFG funded project we optimized a high-content phenotypic-based screening microscopy platform that will be exploited to identify environmental factors (toxins, food component, radiations) acting through mitochondria during animal development to induce neuronal toxicity or promote healthy aging. We validated our platform using genetic and pharmacological interventions known to extend C. elegans lifespan and identified a new mitochondrial ATPase inhibitor with lifespan extending effects. Recently established collaboration with the Haendeler lab and Dr Ralph Menzel are constructively contributing this project.

3. C. elegans models for human mitochondrial-associated diseases (HMAD)

We developed C. elegans models for different HMAD that nicely reproduce disease progression and we are characterizing mitochondrial and neuronal deficits in these models through a combination of behavioral and biochemical assays. The ultimate goal of this project funded by the Strategic Research Funding of the Heinrich Heine University and the DFG is to identify key molecular players of disease pathogenesis for targeted therapeutic interventions (pharmacological, nutritional or natural compounds) to eventually test in corresponding mammalian diseases models. To achieve this last aim we have an established ongoing collaboration with Dr. med. Felix Distelmeir at the pediatric clinic of the HHU Hospital.

Service

The Ventura lab is in charge of the fluorescence microscopy Gurlittstr (Dr. Alfonso Schiavi).

Cooperations

IUF internal:
Haendeler research group
Haarmann-Stemmann junior research group
Krutmann research group
Reinke liaison research group
Schikowski junior research group

National:
Prof. Aleksandra Trifunovic, CECAD Research Center, University of Cologne
Prof. Björn Schumacher, CECAD Research Center, University of Cologne
Prof. Bertram Gerber, Leibniz Institute for Neurobiologiy (LIN) Department Genetics of Learning and Memory, Magdeburg
PD Dr. Felix Distelmeir,  Centre for Child and Adolescent Medicine, University Hospital, Düsseldorf
Dr. Mathias Beller, Institute for Mathematical Modelling of Biological Systems, Heinrich Heine University Düsseldorf
PD Dr. Ralph Menzel, Humboldt-Universität zu Berlin

International:
Prof. Nektarios Tavernarakis, Institute of Molecular Biology and Biotechnology Foundation for Research and Technology-Hellas Medical School, University of Crete, Heraklion, Greece
Prof. Bart Braeckman, Biology Department, Ghent University, Belgieum
Prof. Hilde Nilsen, Institute of Clinical Medicine, University of Oslo, Norway and Department of Clinical Molecular Biology, Akershus University Hospital, Lørenskog, Norway
Prof. Francesco Cecconi, European Center for Brain Research
Santa Lucia Foundation, Rome, Italy & Danish Cancer Society research Center, Cancer Center, Kopenhagen, Denmark
Prof. Jing-Dong J. Han, Shanghai Institutes of Biological Sciences, CAS, China
Prof. Frank Madeo, Institute for Molecular Biosciences, Graz University, Austria

Selected publications

Schiavi A, Maglioni S, Palikaras K, Shaik A, Strapazzon F, Brinkmann V, Torgovnick A, Castelein N, De Henau S, Braeckman BP, Cecconi F, Tavernarakis N, Ventura N: Iron starvation-induced mitophagy mediates lifespan extension upon mitochondrial stress in C. elegans. 25(14): 1810-1822, 2015. [pubmed]

Maglioni S, Arsalan N, Franchi L, Hurd A, Opipari AW, Glick GD, Ventura N: An automated phenotype-based microscopy screen to identify pro-longevity interventions acting through mitochondria in C. elegans. Biochim Biophys Acta-Bioenerg 2015, in press. [pubmed]

Maglioni S, Schiavi A, Runci A, Shaik A, Ventura N: Mitochondrial stress extends lifespan in C. elegans through neuronal hormesis. Exp Gerontol 56: 89-98, 2014. [pubmed]

Schiavi A, Ventura N: The interplay between mitochondria and autophagy and its role in the aging process. Exp Gerontol 56: 147-53, 2014. (Review) [pubmed]

Schiavi A, Torgovnick A, Kell A, Megalou E, Castelein N, Guccini I, Marzocchella L, Gelino S, Hansen M, Malisan F, Condò I, Bei R, Rea SL, Braeckman BP, Tavernarakis N, Testi R, Ventura N: Autophagy induction extends lifespan and reduces lipid content in response to frataxin silencing in C. elegans. Exp Gerontol 48(2): 191-201, 2013. [pubmed]