Descripción del proyecto
Los murciélagos podrían esconder el secreto para una vida más sana y larga gracias a la homeostasis de proteínas
La proteostasis es el equivalente de la homeostasis en las proteínas y consiste en un control preciso de la síntesis, plegamiento, mantenimiento conforme y degradación del proteoma completo de una célula. La batuta para orquestar esta enorme sinfonía no está en manos de un único director, sino de una red de proteostasis compleja y adaptativa. Si esta red no funciona correctamente, pueden aumentar los niveles de proteínas mal plegadas o de agregación, factores asociados con el envejecimiento y ciertas enfermedades neurodegenerativas. El proyecto ComBATageing, financiado con fondos europeos, está estudiando el posible papel de la proteostasis intracelular, en particular la función de la autofagia, en la extraordinaria longevidad de los murciélagos. La autofagia es el proceso proteolítico mediante el cual las células eliminan orgánulos dañados y agregados de proteínas potencialmente tóxicos. Combinados con estudios filogenómicos de la selección adaptativa en los genes asociados con la proteostasis en murciélagos y otros mamíferos, los resultados podrían arrojar luz sobre el papel de la proteostasis en las enfermedades y el envejecimiento normal.
Objetivo
Despite being one of the most familiar biological process affecting our lives, little is known about the molecular mechanics of ageing. A better understanding of ageing and related diseases is today crucial to face its deleterious effects on our growing older population. Among mammals bigger species typically live longer than smaller ones. When corrected for body size, almost all mammals have the same longevity quotients, exception made for the chiroptera. Bats are capable of living up to 10 times longer than expected despite their characteristic high metabolic rates. During my doctorate, I discovered the presence of a distinctive behaviour in bats' autophagic pathway, suggesting that these animals may rely on an improved system for intracellular proteostasis accounting for the flight-associated high metabolic stress. The same evolutive adaptation could ultimately have played a role in allowing bats to achieve exceptional longevity. Here I propose to carry out an in-depth analysis of the proteostatic system, and in particular of the autophagic pathway, in bats. Samples from wild populations of bats will be used to derive primary cell lines allowing to characterise bats’ intracellular phenotype and proteostatic activity. Thanks to the expert personnel and cutting-edge facilities of the hosting institute, I will exploit imaging and proteomics tools to isolate bat-specific molecular features of adaptation in proteostasis and unveil their role in determining their unique ageing pattern. A complementary phylogenomic analysis will be performed to detect traces of adaptive selection in proteostasis-associated genes in bats and other mammals. For the first time, the complexity of interactions behind proteostasis and ageing will be examined from a privileged, integrative perspective. This innovative project holds huge potential as it could lead to a greater understanding of the role of protein homeostasis in mammalian ageing contributing to dampen its effects on our society.
Ámbito científico
Palabras clave
Programa(s)
Régimen de financiación
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinador
20132 Milano
Italia