Aging and Neurodegeneration
Dr. Daniele Bano
Group Leader
Venusberg-Campus 1, Gebäude 99
(ehemals Sigmund-Freud-Str. 27)
53127 Bonn

daniele.bano@dzne.de
 +49 228 43302-510

Areas of investigation/research focus

Aging is the progressive accumulation of damaged macromolecules and cellular structures that negatively impair tissue homeostasis. As a multifactorial biological process, aging inevitably affects organismal fitness and increases susceptibility to infectious and chronic illness, including neurodegenerative diseases. With a demographic shift toward a population with more elderly people, it becomes imperative to develop novel long-term effective strategies that help to ameliorate age-related disorders. Over the last years, exciting studies have described a wide range of pharmacological, dietary and genetic interventions that can promote longevity of multicellular organisms. Given their positive effect on health and stress resistance, the underlying lifespan-extending signaling pathways may be promising targets for treatment of age-related chronic illnesses. Our laboratory explores the interplay between epigenetics, mitochondrial function and metabolism in aging and neurodegenerative disorders. As part of our program, we focus on metabolic changes that occur in animals carrying mitochondrial lesions. Furthermore, we study those epigenetic regulators that promote transcriptional flexibility underlying lifespan-extending programs and environment-induced metabolic adaptations. Our final goal is to define the relevance of these factors in the onset and progression of neurodegenerative processes. Additionally, using genetic and pharmacological approaches, we aim to unveil molecular targets and perform proof-of-principle compound screenings with potential applications in preclinical studies.

 more Infos

Mitochondrial dysfunction. We study the importance of mitochondrial bioenergetics in cellular metabolic responses. Our previous work elucidated novel mitochondria-dependent molecular cascades that contribute to cell death and neuronal dysfunction (Sendoel A. et al, 2014; Gioran A. et al, 2014; Meyer K. et al, 2015). In the context of human pathologies causally linked to mitochondrial dysfunction, we search for new molecular players that can counteract mitochondrial lesions and ameliorate the associated degenerative processes. As part of our translational effort, we perform in vitro and in vivo screenings of biologically active molecules. Potential candidate compounds are currently being tested for their beneficial effects on survival and fitness of nematodes as well as mice carrying mitochondrial defects. This may open avenues for neuroprotective strategies.

Epigenetic plasticity and neurodegenerative processes. We aim to understand the epigenetic mechanisms underlying age-related processes in metazoans. We have recently demonstrated that the replication-independent histone variant H3.3 enables C. elegans longevity pathways through the maintenance of transcriptional plasticity (Piazzesi A. et al, 2016). Next, we are going to further our investigation into the epigenetic factors that could unify these aging modifiers. Our work extends also to other aspects of chromatin remodeling. Specifically, we are interested in understanding the importance of the SWI/SNF/BAF complex in age-related neurodegenerative conditions. As part of our program, we will explore how aberrant SWI/SNF/BAF complex activity can enhance neuronal vulnerability in animals challenged by metabolic and environmental insults.   

Schlüsselpublikationen

Anna Gioran, Antonia Piazzesi, Fabio Bertan, Jonas Schroer, Lena Wischhof, Pierluigi Nicotera, Daniele Bano. Multi-omics identify xanthine as a pro-survival metabolite for nematodes with mitochondrial dysfunction. EMBO Journal. 2018 Dec 31; doi: 10.15252/embj.201899558
Lena Wischhof, Anna Gioran, Dagmar Sonntag-Bensch, Antonia Piazzesi, Miriam Stork, Pierluigi Nicotera, Daniele Bano. A disease-associated Aifm1 variant induces severe myopathy in knockin mice. Molecular Metabolism. 2018 Jun 30; 13:10-23. doi: 10.1016/j.molmet.2018.05.002
Lena Wischhof, Simona Maida, Antonia Piazzesi, Anna Gioran, Kristina Barragan Sanz, Stephan Irsen, Marc Beyer, Joachim L. Schultze, Martin J. Dyer, Paolo Salomoni, Dan Ehninger, Pierluigi Nicotera, Daniele Bano. The SWI/SNF subunit Bcl7a contributes to motor coordination and Purkinje cell function. Scientific Reports. 2017 Nov 30; 7 doi: 10.1038/s41598-017-17284-3
Piazzesi A, Papić D, Bertan F, Salomoni P, Nicotera P, Bano D. Replication-Independent Histone Variant H3.3 Controls Animal Lifespan through the Regulation of Pro-longevity Transcriptional Programs. Cell Rep. 2016 Oct 18; 17:987-996. doi: 10.1016/j.celrep.2016.09.074
Meyer, Buettner, Ghezzi, Zeviani, Bano, Nicotera. Loss of apoptosis-inducing factor critically affects MIA40 function. Cell Death and Disease. 2015 Jun 30; 6 doi: 10.1038/cddis.2015.170
Ataman Sendoel, Simona Maida, Xue Zheng, Youjin Teo, Lilli Stergiou, Carlo-Alberto Rossi, Deni Subasic, Sergio M. Pinto, Jason M. Kinchen, Moyin Shi, Steffen Boettcher, Joel N. Meyer, Markus G. Manz, Daniele Bano, Michael O. Hengartner. DEPDC1/LET-99 participates in an evolutionarily conserved pathway for anti-tubulin drug-induced apoptosis. Nature Cell Biology. 2013 Dec 31; 16:812-820. doi: 10.1038/ncb3010

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