Pamela
A.
Silver
Department
of
Systems
Biology,
Harvard
Medical
School
and
The
Wyss
Institute
for
Biologically
Inspired
Engineering,
Harvard
University
The engineering of Biology presents infinite opportunities for therapeutic design, diagnosis, and prevention of disease. Towards these goals, we seek to make the engineering of Biology faster, more predictable and cheaper. This ‘Synthetic Biology’ has deep practical and social consequences for the pharmaceutical as well as the commodity industry. Here, I will present concepts and experiments that begin to address how we approach these problems in a systematic way.
By one strategy, we seek to predictably engineer mammalian cells to produce novel compounds that could potentially act as new therapeutics. For example, we have developed an algorithm for biosynthesis of new steroids that could have increased specificity towards their respective targets. This has implications in treatment of inflammation and clean production of other chemicals of interest.
By a second strategy, we design chimeric proteins to act as specific therapeutics. Specificity in biologics remains one of the outstanding issues in their use. We have again developed an algorithm based on coarse grain modeling for the predictable design on new proteins. Some have been tested in animals and show the predicted effects.
Lastly, we engineer components of the microbiome to act as both diagnostics and therapeutics. In one example, we have engineered natural gut bacteria to record the exposure of animals to antibiotics and to count the number of cell divisions as the bacteria passes through the gut. We can engineer the same bacteria to secrete toxins that could result in localized killing of pathogens and to act in a communal manner. Taken together, these experiments have far-reaching implications for the use of biology to prevent and treat disease in the future.