Principes de l’évolution du réseau de l’homéostasie des protéines
Cell homeostasis is the ability of a cell to maintain its balance and functionality. One of the causes of the instability of this balance is stress. Indeed, stress causes an accumulation of misfolded proteins, which can form aggregates causing neurodegenerative diseases. Molecular chaperones are the main cellular mechanism that promote protein folding and quality control. These form the heart of a network called protein homeostasis network. The purpose of this is to control, insure and protect the proteome through folding and elimination of aggregates. The network plays a vital role in keeping cellular protein in homeostasis known as proteostasis. Failure of protein homeostasis is linked to aging and aging-associated neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Currently, our understanding how this network keeps the proteome in balance in health, and how it fails and causes diseases, remains incomplete. Different species offer striking examples. For instance, the naked-mole rate, Heterocephalus glaber, remarkable for its life expectancy of over 30 years, it has an effective stress-resistant mechanism and a good homeostasis, which allows it to easily achieve a balance and homeostasis. On the other hand, the killifish, Nothobranchius furzeri, whose life expectancy is very short, has an accelerated aging process and with pronounced loss of homeostasis. Here we seek to ask, how does this balance work for these and other organisms? This research project will use bioinformatics and comparative genomics approaches to highlight the fundamental principles of proteostasis. The evolution of the chaperone network will be analyzed in the context of proteome adaptation. We analyze the diversification of the chaperone network across the eukaryotic phylogeny and compare it with aspects of the evolution of the corresponding proteomes. This master's project provide fundamental insights into the biology and the evolution of the protein homeostasis network. Moreover, we use comparative genomics analysis of chaperons from 216 eukaryotes species which indicates that the balance in proteostasis could be a key variable in explaining organismal robustness.
Evolution chaperons homeostasis bioinformatics phylogenetics