Dr. Manuela Antonioli
Cell. and Mol. Biology
Junior Fellow (Marie S. Curie FCFP)
September 2015 - August 2016
Center for Biological System Analysis (ZBSA),
University of Freiburg
79104 Freiburg Germany
Manuela Antonioli is a post-doctoral researcher who has been working both at the National Institute for Infectious Diseases L. Spallanzani, Rome (for Prof. Gian Maria Fimia) and at the University of Rome ‘Tor Vergata’ (for Prof. Mauro Piacentini) since 2007. Since undergraduate, she addressed to the field of autophagy. During the Ph.D., she published the characterization of the dynamic interaction between AMBRA1 and dynein motor complex during autophagy induction (Di Bartolomeo et al., 2010). At the same time, she started to collaborate with Prof. GM Fimia (INMI, IRCCS ‘L. Spallanzani’) and with Prof. J. Denjel (FRIAS Institute in Germany) aimed at characterizing the AMBRA1 interactome using a TAP approach associated to mass spectrometry analysis. Following the Ph.D., she started the post-doc working with Prof. GM Fimia focusing on different aspects arose from the AMBRA1 protein-protein interactions study. In particular, she was deeply involved in characterizing the interplay between AMBRA1 and Cullin E3 Ubiquitin ligases in the regulation of autophagy dynamics (Antonioli et al., 2014). Moreover, she has been collaborating with Prof. F. Cecconi in further defining AMBRA1 functions in autophagy and cell proliferation (Nazio et al., 2013, Cianfanelli et al., 2014). She attended at several international congresses, often as a selected speakers and she acts as a reviewer for journals including PLOS ONE and Cell Death Disease.
- Antonioli, M., Albiero, F., Nazio, F., Vescovo, T., Perdomo, A.B., Corazzari, M., Marsella, C., Piselli, P., Gretzmeier, C., Dengjel, J., et al. (2014). AMBRA1 Interplay with Cullin E3 Ubiquitin Ligases Regulates Autophagy Dynamics. Dev. Cell 31, 734–746.
- Di Bartolomeo, S., and Corazzari, M. (2010). The dynamic interaction of AMBRA1 with the dynein motor complex regulates mammalian autophagy. J. Cell Biol. 191, 155–168.
- Cianfanelli, V., Fuoco, C., Lorente, M., Salazar, M., Quondamatteo, F., Gherardini, P.F., De Zio, D., Nazio, F., Antonioli, M., D’Orazio, M., et al. (2014). AMBRA1 links autophagy to cell proliferation and tumorigenesis by promoting c-Myc dephosphorylation and degradation. Nat. Cell Biol. 17, 20–30.
- Fimia, G., Corazzari, M., Antonioli, M., and Piacentini, M. (2012). Ambra1 at the crossroad between autophagy and cell death. Oncogene 32, 3311–3318.
- Nazio, F., Strappazzon, F., and Antonioli, M. (2013). mTOR inhibits autophagy by controlling ULK1 ubiquitylation, self-association and function through AMBRA1 and TRAF6. Nat. Cell Biol. 15, 406–416.
In vivo study of the protein interaction network on lysosomes during starvation
Understanding the molecular links between macroautophagy and chaperone-mediated autophagy (CMA) is the central goal of the proposed project. In almost all mammalian cells, three autophagic pathways exist, i.e. macroautophagy, microautophagy and CMA. These are catabolic processes that use lysosomes for the degradation of cellular components to maintain homeostasis and energy production. In particular, macroautophagy and CMA mainly differ for the specificity of degrading substrates and their import into the lysosomal lumen. Despite active cross talk between these catabolic pathways has been described, the molecular connections between them are still unknown. To investigate this aspect, an in vivo study of differential lysosomal complexes during starvation will be performed by APs-mass spectrometry. Based on results obtained from the proteomics analysis, we will perform different cellular and molecular approaches to understand the function of identified complexes. Considering the involvement of macroautophagy and CMA in neuronal differentiation and homeostasis, achievement of this project will not only allows a deep understanding of autophagy, but could also provide new insights into human neurodegenerative diseases.