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Hadley D. Sikes Lab | Research Projects

 

Enzyme engineering

Biological catalysts are truly remarkable.  Enzymes perform challenging chemical transformations under mild and environmentally friendly conditions with an unrivaled degree of specificity and selectivity.  Stability (thermal, chemical, operational) and cost are often cited as barriers to the technological application of enzymes.  However, successful commercial examples such as proteases in laundry detergents and glucose oxidase in glucose monitors provide evidence that these barriers can be overcome with ingenuity and systematic engineering.
Modern protein engineering techniques such as structure-guided recombination and directed evolution can be used to create new enzymes with desirable activity, stability, and cost from naturally occurring starting points that do not possess these desirable attributes.  We engineer enzymes for medical applications (therapeutics, diagnostics), for use in synthetic biology, and for energy applications.   In addition to practical applications, we are interested in using our directed evolution data sets, a host of biophysical techniques, and insights from molecular simulations to further understanding of sequence/activity relationships.


Polymerization-based amplification

Inexpensive, robust strategies for detecting molecular recognition events are in great demand in diverse fields such as medical diagnostics, environmental monitoring, food safety, and defense.  Techniques that show promise in laboratory settings often do not meet the rigorous demands of real-world applications.  In many cases, tolerance for complex analyte solutions, assay time, sensitivity, ease of use, incidences of false positives and false negatives, cost and complexity of instrumentation (if any), and cost and shelf-stability of reagents are all of supreme importance.  Weaknesses in even one category can severely limit the impact of a technique.  In this context, we are designing, synthesizing and characterizing dual-functional macromolecules that are capable of molecular recognition and of initiating polymerization reactions, and we are testing these molecules in a variety of exciting real-world applications.


Electrode-driven biocatalysis

An interest in electrode-driven biocatalysis unites many fields that may not appear to be related at first glance:  industrial scale synthesis, energy storage and conversion, biomedical diagnostics.  Some enzymes are amenable to immobilization on electrodes in a catalytically active state, but many are not.  Though electrical communication between electrodes and active sites can often be established, substrate turnover capability is lost.  We are addressing this long-standing problem in a variety of molecular systems using a combination of interfacial engineering, protein engineering, and attention to the mechanistic details of enzymatic catalysis.


 

 

 

 

MIT - ChemE, 77 Massachusetts Ave, E19-502C, Cambridge, MA 02139 | Email: sikeslab-www@mit.edu | Updated: March 2, 2011