The goal of this project is to implement a new method
to optimize protein crystallization to eventually study
the structures of membrane proteins and G-protein couple
receptors. Although protein crystallography is the most
successful technique for structure determination, membrane
proteins present challenges to crystallization. Human
membrane proteins represent about 30% of the genome,
and about 50% of drug targets, but only about 100 membrane
protein structures have been determined to date, comparted
to tens of thousands of water-soluble proteins. The
number of crystallization trails is limited by the avialability
of human proteins, which typically do not express well
in bacteria. Brandeis is developing microfluidic methods
to crystallize membrane proteins, including ion channels
and G-protein-coupled receptors. Researchers at Brandeis
are developing a high throughput, low volume microfluidic
device called the Phase Chip. The Phase Chip consists
of an elatomeric polymer on which different microfluidic
components will be fabricated and interconnected to
precisely meter, mix, and store sub-nanoliter amounts
of sample, solvent, and other reagents.
This method solves a major problem in protein crystallization,
the decoupling of nucleation from growth. IGERT trainees
will work on the development of this technology as well
as use it to study the structure of membrane proteins.
