Abstract
The goal of this project is to set up a framework where the study of complex signalling events (classically investigated by cell biology) can be supported by an in-silico approach in a time and cost-effective fashion. We will generate an in-silico model to investigate tissue-specific functions of signalling proteins. In particular the ROCO proteins (LRRK1, LRRK2, DAPK1 and MASL1). During the project the student will develop both advanced systems biology knowledge (i.e. bioinformatics, protein-interaction and gene co-expression network analysis) and molecular/biochemical skills focused on protein production/handling and proteo-array analysis.
References
Genome, transcriptome and proteome: the rise of omics data and their integration in biomedical sciences. Manzoni C, et. al. Brief Bioinform. 2018 Mar 1;19(2):286-302. doi: 10.1093/bib/bbw114
Integrating protein networks and machine learning for disease stratification in the Hereditary Spastic Paraplegias, Vavouraki N, et. al. iScience. 2021 May 21; 5:102484. doi.org/10.1016/j.isci.2021.102484
Comparative Protein Interaction Network Analysis Identifies Shared and Distinct Functions for the Human ROCO Proteins. James E. Tomkins, Sybille Dihanich, Alexandra Beilina, Raffaele Ferrari, Nicolò Ilacqua, Mark R. Cookson, Patrick A. Lewis, Claudia Manzoni. Proteomics, 2018. doi.org/10.1002/pmic.201700444
Stratification of candidate genes for Parkinson’s disease using weighted protein-protein interaction network analysis. Ferrari R, et al. BMC Genomics. 2018 Jun 13;19(1):452. doi: 10.1186/s12864-018-4804-9.
LRRK1 Phosphorylation of Rab7 at S72 Links Trafficking of EGFR-containing Endosomes to Its Effector RILP. Hiroshi Hanafusa, Takuya Yagi, Haruka Ikeda, Naoki Hisamoto, Tomoki Nishioka, Kozo Kaibuchi, Kyoko Shirakabe, Kunihiro Matsumoto. Journal of Cell Signalling, 2019. doi: 10.1242/jcs.228809
Genetic, Structural, and Molecular Insights into the Function of Ras of Complex Proteins Domains. Laura Civiero, Sybille Dihanich, Patrick A. Lewis, Elisa Greggio. Chemistry and Biology, 2014. doi: 10.1016/j.chembiol.2014.05.010