Membrane Protein Folding
Protein folding is a fundamental process of life with important implications throughout biology. Elaborate mechanisms exist to regulate and assist folding. Moreover, tens of thousands of mutations have now been associated with diseases and it is thought that most of these mutations affect protein folding and trafficking rather than function. Consequently, there has been an enormous effort over the years to understand how proteins fold. Essentially all of the effort has been directed at soluble proteins, however, and membrane proteins have been largely shunted aside. The lack of effort has not occurred because membrane proteins are unimportant or uninteresting, but because of the great technical challenges they present. It is a challenge that we must overcome if we ever hope to understand membrane biology and disease mechanisms involving a large fraction of the protein universe. We are working to understand folding mechanisms and to develop techniques to study folding and expand the field.
Synthetic Biochemistry for Biofuels and Green Chemical Production
Considerable effort is currently directed to engineer micro-organisms to produce useful chemicals. The greatest potential environmental benefit of metabolic engineering would be the production of high volume commodity chemicals, such as biofuels. Yet the high yields required for the economic viability of low-value chemicals are particularly hard to achieve in microbes due to the myriad competing biochemical pathways. We are developing an alternative approach, which we call synthetic biochemistry. Synthetic biochemistry throws away the cells and builds biochemical pathways in reaction vessels using complex mixtures of isolated enzymes. As the only pathway in the vessel is the desired transformation, yields can approach 100%. The challenge for synthetic biochemistry is to replace the complex regulatory systems that exist in cells in a simplified form. We are designing and testing various ideas for building highly robust systems that can operate continuously for long periods of time.