The cerebrum, as the substrate for our consciousness, memories, personality, and self-identity, presents unique challenges for regenerative medicine. Regenerative approaches must not only maintain general cerebral function, but also preserve as much as possible the details of the wiring and firing parameters that define each individual. A combination of molecular repair and gradual cellular replacement appears most likely to succeed. Toward this end, we are establishing paradigms in mice for replacing glutamatergic projection neurons in the neocortex, seat of our highest cognitive functions.

A major roadblock to successful organ bioengineering is the need for a functional vascular network within the engineered tissue. Here, we describe the fabrication of three-dimensional, naturally derived scaffolds with an intact vascular tree. Livers from various species were perfused with detergent to selectively remove the cellular components of the tissue while preserving the extracellular matrix components and the intact vascular network.

We are improving DNA sequencing to achieve our goal of turning biology into an information science. Along the way, various SENS approaches will be accelerated by improved DNA sequencing, and we present here specific experimental paths for using the tool in service of SENS. As one example, sequencing offers extreme technical shortcuts in molecular directed evolution techniques, allowing larger populations to be interrogated with fewer rounds of evolution and increased stringency of selection.

Humanity is on the cusp of an exciting longevity revolution. The first person to live to 150 years has probably already been born. What will your life look like when you live to be over 100? Will you be healthy? Will your marriage need a sunset clause? How long will you have to work? Will you finish one career at 65 only to go back to school to learn a new one? And then, will you be happily working for another sixty years? Maybe you'll be a parent to a newborn and a grandparent at the same time. Will the world become overpopulated?