Title: The Origins of Life: An uncanny resemblance to the old Protein Folding Problem
Abstract: How did the first living cells come into being from the earth's molecular soup 3.5 billion years ago? Despite much speculation - maybe RNA came first, or proteins, or chemical networks - there's not yet a consensus origins story. New insights are coming from thinking not just about life's molecules, but about biology's process of adaptation. The Darwinian evolution process must have preceded the origins of life. This, and the apparent needle-in-a-haystack nature of sequence space, indicate a key role of proteins in life's origins.

Title: How Hsp70 molecular chaperones recognize substrates that need their help: Selective promiscuity
Abstract: Successful folding of proteins in the cell and their delivery to appropriate destinations are challenging processes. Incompletely folded proteins are sticky, causing them to be prone to inappropriate interactions and aggregation, problems now recognized to underlie many pathologies, especially neurodegenerative diseases. A complex system of molecular chaperones and degradation machines operates in the cell to mitigate against protein misfolding diseases. The maintenance of protein homeostasis, or proteostasis, relies on the ability of chaperones and degradation machines to bind to proteins that need their help to fold to their native states or are irrevocably misfolded. We have sought to understand the basis of the recognition of substrates by the highly prevalent and multifunctional molecular chaperones, the Hsp70s. The most amazing aspect of the protein homeostasis network is that it acts on the entire proteome. Hence, chaperones must have promiscuous binding. However, it is crucial that chaperones only bind to those proteins that are incompletely folded. In this talk, I will describe how the use of peptides as models for regions of proteins that act as recognition sites has provided insight into the basis of selective promiscuity in Hsp70 chaperone/substrate binding.