Kenneth G. Miller, Ph.D.

Assistant Member, Molecular and Cell Biology Research Program

B.S., Houghton College, Houghton, NY,1985
Ph.D., Stanford University, Stanford, CA, 1993
 
Joined OMRF Scientific Staff in 1993.
Curriculum Vitae
 
e-mail: Kenneth-Miller@omrf.ouhsc.edu
office:  (405) 271-1826
lab:  (405) 271-1827

The goal of my research is to understand the molecular signaling network that regulates the transfer of information between nerve cells, a process known as synaptic transmission. During synaptic transmission, various small molecule neurotransmitters are secreted at specialized sites known as synapses, which are arranged along nerve cell processes and are packed together at amazingly high densities in the brain. Synapses can be thought of as biological transistors that must function as relays for all aspects of behavior, learning, and memory. The amount of synaptic transmission that occurs at synapses is highly regulated, and understanding this regulation should provide insights into the chemical reactions from which our thoughts, perceptions, and movements are born.

Diagram of a chemical synapse.

Synapses in the model organism C. elegans (a roundworm) appear virtually identical to synapses in the human brain. The simplicity of the C. elegans nervous system, combined with an astounding repertoire of molecular, cellular, and genetic tools, makes this organism an ideal choice for identifying the genes that are important for regulating synaptic transmission. In recent years, our research in C. elegans, along with that of several other labs, has revealed a complex molecular signaling network that is required for synaptic transmission. The individual components of this network are conserved in humans and are found in all nerve cells. For these reasons, we believe that this Synaptic Signaling Network is perhaps the core system that nerve cells use to turn synapses ON and OFF.

Our studies prior to this year had only provided tantalizing clues about the precise nature of the Synaptic Signaling Network. For example, we knew that the network was centered around at least two “G proteins” that function as chemical ON/ OFF switches to control synaptic transmission. With the aim of discovering additional components of the network, we undertook two large genetic screens for mutants in which the Synaptic Signaling Network was in some way disrupted. Although our analysis of the new mutants is still far from complete, the combined screens have already yielded important new clues, including the identification of another major branch of the network composed of a third G protein pathway. In the past year, we have been using genetic methods to investigate the relationships between the 3 major G protein pathways as well as continuing to map our large collection of mutants in hopes of identifying other proteins that function in the network. By providing a glimpse of the molecular circuitry for turning synapses ON and OFF, these studies are helping to unlock the wonderful mysteries of the brain, as well as providing a firm foundation for the investigation of human neurological disorders.
 
For a slide presentation of Ken Miller's research, click on the Recent Presentations link below.
 

Full Text links may require journal subscription.

Miller, K.G., Alfonso, A., Nguyen, M., Crowell, J.A., Johnson, C.D., and Rand, J.B. (1996). A Genetic Selection for Caenorhabditis elegans Synaptic Transmission Mutants. PNAS 93, 12593-12598.
   Abstract | Full Text
 
Miller, K.G., Emerson, M.D., and Rand, J.B. (1999). Goa and Diacylglycerol Kinase Negatively Regulate the Gqa Pathway in C. elegans. Neuron 24, 323-333.
   Abstract | Full Text
 
Miller, K.G., Emerson, M.D., McManus, J.B., and Rand, J.R. (2000). RIC-8 (Synembryn): A Novel Protein that is Required for Gqa Signaling in the C. elegans Nervous System. Neuron 27(2), 289-299.
   Abstract | Full Text
 
Miller, K.G. and Rand, J.B. (2000). A Role for RIC-8 (Synembryn) and GOA-1 (Goa) in Regulating a Subset of Centrosome Movements During Early Embryogenesis in C. elegans. Genetics 156, 1649-1660.
   Abstract | Full Text

West Coast C elegans Meeting- August 2002

Mutations that Activate the Gsa Pathway Bypass the Neurotransmitter Release Blockade in ric-8(md303) and Reveal Another Branch of the Synaptic Signaling Network
 

Faculty Retreat Talk- March 2001

Signaling Pathways that Regulate Synaptic Transmission
 

West Coast C elegans Meeting 2000

RIC-8 (Synembryn): A Novel Protein that is Required for Gqa Signaling in the C. elegans Nervous System.

Genetics Society of America