Research

We are interested in using chemical methods to understand problems in neurobiology and development, as well as exploiting neurobiology to construct biosensors. In general, answers to the biological questions addressed by the group are not accessible using traditional biological techniques. As a result, the group makes use of chemical approaches and a variety of tools to gain new insights into complex biological problems. The tools we use to address these problems include synthetic organic chemistry, surface chemistry, biochemistry, molecular biology, and cell biology. Although a group member may focus on one skill set, it is expected that they will have a working knowledge of several different areas.

Neuronal Wiring and Development. Our brains consist of an enormous number of neurons that interact with each other in very specific and complex ways to give rise to human thought and function. Neurons within this network are guided to make specific connections through a variety of chemical signals that include small molecules, soluble proteins, and proteins presented on the surface of other cells. We are interested in developing minimal models to understand neuronal guidance by spatially patterning guidance cues. Patterning is achieved through the creation of photopatternable self-assembled monolayers (SAMs) on gold, aluminum oxide, and titanium oxide. The use of organic photochemistry allows multiple proteins to be easily presented on a single culture surface. Our chemical approach to this problem allows us to build complex model neuronal networks that cannot be achieved using traditional methods.

Ion-Channel Biosensors. New threats of chemical and biological terrorism have created the need for new classes of biosensors to monitor and ensure the safety our water supply. Ligand-gated ion channels detect low levels of aqueous organic molecules by directly generating a measurable electric current. Additionally, protein molecules have been shown to exquisitely distinguish between subtly different organic molecules, making proteins an ideal choice for toxin recognition. To develop field-rated ion-channel biosensors, we are taking a multi-pronged approach. First, surface chemistry is being employed to develop stable devices for recording ion-channel electrical activity. This is necessary since the existing methods of measuring ion-channel currents are extremely delicate. Secondly, a bacterial ion channel is being genetically altered to sense chemical toxins using novel surface chemistry based screening technologies. Finally, we are developing biomimetic ion channels and lipid bilayers to produce ion-channel biosensors that lack the inherent instabilities associated with biological molecules.

Neuronal Differentiation. The ability to repair damaged neuronal tissue could potentially help millions of people suffering from brain and nervous system disorders. For example, transplantation of fetal dopaminergic neurons can be used to treat Parkinson's disease, although both ethical and technical limitations prevent this. Embryonic stem cells provide a potential renewable source of neurons for transplantation. However, differentiation of stem cells has been hindered by the failure of traditional biochemistry to find the molecular determinate for dopaminergic neuron formation. We seek to identify this determinate by combining biochemistry with surface chemistry. We are interested in using chemical methods to understand problems in neurobiology and development, as well as exploiting neurobiology to construct biosensors. In general, answers to the biological questions addressed by the group are not accessible using traditional biological techniques. As a result, the group makes use of chemical approaches and a variety of tools to gain new insights into complex biological problems. The tools we use to address these problems include synthetic organic chemistry, surface chemistry, biochemistry, molecular biology, and cell biology. Although a group member may focus on one skill set, it is expected that they will have a working knowledge of several different areas.

Selected Publications

• J.A. Maurer and D.A. Dougherty, "Generation and evaluation of a large mutational library from the E. coli mechanosensitive channel of large conductance, MscL. Implications for channel gating and evolutionary design," J. Biol. Chem., 278, 21076 (2003).
• J.A. Maurer and D.A. Dougherty, "A high-throughput screen for MscL channel activity and mutational phenotyping," BBA Biomembranes., 1514, 165 (2001).