1: Systems level analysis of protein synthesis in live animals.

We will:

• Utilize novel applications of ribosome profiling to characterize protein synthesis in various organs of mice;

• Identify alternative start codons and define protein isoforms in these organs; and

• Apply these approaches to naked mole rats, which are mouse-sized rodents that live 10 times longer than mice.

2: Determine rates and features of protein synthesis in various organs in a species-, organ-, protein-, and diet-specific manner.

We will:

• Determine rates of protein synthesis at the level of organs and individual proteins in mice and naked

mole rats;

• Characterize regulation of protein synthesis by age and calorie restriction, as well as their influence on

footprint length, ribosome density, metagene properties, ribosomal pauses, and different protein

isoforms; and

• Characterize parallel regulation of protein expression at the level of transcript abundance and protein

synthesis in the organs of mammals.