The Audacious Project

THE PROBLEM
Proteins are the molecular machines that make all living things hum. They stop deadly infections, heal cells, capture energy from the sun and so much more. Proteins are built by stringing together chemical building blocks, called amino acids, according to instructions in an organism’s genome. These strings then ‘fold up,’ based on the chemical forces between the amino acids, to form the complex three-dimensional structures needed to perform specific jobs. Although nature has been building proteins for more than 3 billion years, the number of possible proteins is astronomical: There are more ways of assembling 100 amino acids than there are atoms in the universe. For years, scientists have tried to predict the shapes protein molecules should assume based on their amino acids — with limited success. This is known as the “protein-folding problem.” Because of its elusive nature, understanding how to harness the power of proteins to solve problems has remained a mystery.

BIG IDEA
Over the past 20 years, David Baker’s team has studied the rules of protein folding and encoded them in Rosetta, a computer simulation that’s driven big breakthroughs in understanding how proteins form their structure. Now, for the first time in human history — thanks to the technological convergence of Rosetta, the rise of inexpensive computing and the genomic revolution in reading and writing DNA — researchers at the UW School of Medicine’s Institute for Protein Design (IPD) can design new proteins from scratch with functions never before seen in nature. With investment made through The Audacious Project, the IPD will expand its ability to design new proteins and endeavor to fundamentally change how drugs, vaccines, fuels and new materials are made throughout the world.

PLAN
The core of this plan is to make IPD the Bell Labs of protein design. During its heyday in the 1950s, Bell Labs drove the innovations that laid the foundations of the modern digital era. The collaborative environment of Bell Labs attracted top research talent and made it a hotbed of scientific discovery and technological achievement. Just as Bell Labs helped create the digital revolution, the Institute for Protein Design will work to fuel the protein design revolution. By expanding the institute, increasing the number of personnel and training a new generation of scientists, IPD will accelerate the pace of discovery and dissemination of new protein technology. Their work will focus on five grand challenges:

1. A universal vaccine for the flu, and vaccines for HIV and cancer.
2. New drug candidates for chronic pain and neurodegenerative diseases.
3. Advanced delivery vehicles for genetic diseases.
4. Smart protein therapeutics.
5. The creation of nanomaterials related to solar energy and other manufacturing needs.

 
WHY WILL IT SUCCEED?
Located at the UW School of Medicine in Seattle, the IPD leads the field of computational protein design. The institute has already created synthetic proteins that bind viruses to protect against infection and have pioneered protein-based containers that package and deliver genetic instructions to cells. These advances indicate great potential for smart protein therapeutics. Recent successes with new, better flu vaccines that program the immune system to fight multiple strains of the virus are paving the way for universal vaccine opportunities. Additionally, the IPD already has experience bringing their discoveries to market, spinning off multiple biotech companies in the last few years.