Jan 28

Crowdsourcing the design of new molecules to improve healthcare and the environment

John Foy and I recently visited the The University of Washington’s Institute for Protein Design (IPD) as part of the Seattle Health Innovators program committee’s effort to build bridges between the downtown Seattle tech startup community and the biotechnology and biomedical luminaries in the area.  The UW Medicine Advancement Office was kind enough to make arrangements for us to visit the lab in mid-January.Ed and John at IPD

IPD scientists are designing synthetic proteins to help with diagnostics, therapeutics, CO2 fixation, and to create new drug delivery platforms.  We spoke with scientists working on new drug delivery mechanisms to treat cancer, neurological disorders, and influenza.

In addition to having brilliant scientists on staff, they are using a volunteer network that makes available unused processing power of idle computers and also taps the brainpower of gamers who enjoy folding proteins in an online game.

David Baker is head of the IPD and gave us a tour of the eponymous Baker Laboratory that combines computer modeling, synthetic DNA, and the output of living biological organisms. The Baker Lab created  the Rosetta software suite for predicting and Rosetta proteindesigning protein structures, protein folding mechanisms, and protein-protein interactions. The analysis is computationally intensive, requiring massive computer resources. This has been accomplished through the  Rosetta@home community of over 370,000 participants.  This enables all these people to make their computers available to support this ground-breaking research.

In addition to Rosetta, the lab has created Fold-It, an online protein folding game that encourages users to “solve puzzles for science”. This game now has a global community with teams competing with each other for designing new shapes that may be relevant to diseases including HIV/AIDS, cancer, and Alzheimer’s. According to Dr. Baker, even non-biochemists have been able to use fold-it  to not only increase their understanding of proteins but also to make significant progress in discovering new self-assembling shapes that may have practical use.

The Baker lab itself is remarkable.  Entering the lab one sees a space divided in half. On the left is a studio of designers Baker lab software engineersworking at their desks with large monitors. It looked like a dozen other design studios I have seen in Seattle. But on the right, visible through the glass wall, was a biochemistry lab, with counters full of equipment and shelves packed with clear jars of mysterious fluids and bacteria cultures.

The protein designers work with Rosetta software to come up with a hypothetical design for how a protein molecule with a desired self-assembling structure could be constructed from a sequence of specific amino acids. The software then allows the Institute to order the genes for that sequence to be created by a DNA lab.  When the synthesized DNA comes back they put it into bacteria which then produce the new protein structures. Baker wet labThis allows the Institute to discover which of their designs can actually work in the physical world.  Electron microscopy can magnify these new proteins to view the new structures at the atomic level. These images can be quite beautiful, as can be seen in the video link below.

The scientific mission of the institute has been funded through a variety of public and private grants. However, the Institute is also an incubator of new biotech startups.  We spoke with Neil King, a post-doctoral fellow who plans to launch a company to commercialize a new protein that can be used as a platform for drug delivery. It has an elegant structure that allows a drug payload, such as a chemotherapy drug, to be sent harmlessly John Foy, Ed Butler, Neil Kingthrough the body until it connects with a targeted cell, whereupon it releases the drug only to that cell. This mechanism could open new possibilities for targeted therapies for cancer and Alzheimer’s.  Another project at the Institute is a protein that can attach to the influenza virus. The commercial potential of a more effective way to treat people with influenza is  very promising.

The Seattle area is home to spectacular innovation in health and life sciences. This is an emerging trend that builds on Puget Sound’s aerospace and information technology base. At the IPD we saw that the boundaries between computer science, healthcare, energy, materials science, and life sciences are becoming harder to draw.

For more information about the Institute for Protein Design, including images of some of their molecules see their Facebook page.  For a more detailed explanation directly from David Baker, see this link from the UW Molecular Engineering & Sciences Symposium, 2013.


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