The Early Years
As a biochemistry major, John discovers Peter Mitchel's Chemiosmosis Theory.
1980-1981 Senior thesis research in the laboratory of Dr. R.C. Fuller: "Chemiosmotic coupling in Chloroflexus aurantiacus"
The obvious result from combining my interest in neurobiology with the idea that membrane ion transport is important is an interest in the ion channels that make the electrical activity in neurons.
In 1981, the biochemistry of ion channels is almost non-existant.
John becomes interested in the idea that it should be possible to isolate, characterize, and reconstitute the voltage-sensitive sodium channel from brain.
Once in Seattle, John learns that other grad students are already working on sodium channel isolation, characterization, and reconstitution. With the support of the NSF, John gets to study how a brain cell makes a sodium channel.
John swims in the frothy sea of primary brain cell culture and wishes there were better brain cell lines.
Down the hall from Ed Krebs, John gets exposed to the idea of regulating the functional activity of ion channels by means of the covalent modification called protein phosphorylation.
Why not attempt to understand memory and learning in the brain in terms of the regulation of synaptic function and structure?
John decides to try to use the newly identified Oncogenes to engineer better brain cell lines for facilitating research on synaptic biochemistry.
John stumbles onto the fact that the vSRC tyrosine kinase can disrupt normal cell-to-cell adhesion.
This idea suggests that tyrosine phosphorylation and regulation of cell adhesion might be important for cancer biology, but John's first attempt to obtain funding as an independent investigator in the area of adhesion and cancer gets nowhere. Subsequently, cadherins become a big deal in cancer biology.
John decides that regulation of cadherin cell adhesion molecule function my means such as tyrosine phosphorylation is a possible mechanism for both the establishment of neural networks and the mechanism of long-term memory by means of altering synaptic connections in response to on-going synaptic activity. When I was still a postdoc at the end of 1992 I submitted a proposal for independent research funding in the area of neuronal cadherin research: the goal was to determine if cadherins really are located in synapses and if so, to begin to test their role in learning and long-term memory storage. My proposal was not funded, but eventually I was funded to develop a confocal microscopy facility with which I could visualize synaptic concentrations of adhesion proteins. Others such as folks in Takeichi's lab were able to use E.M. studies to shown that cadherins have an interesting distribution in synapses (The catenin/cadherin adhesion system is localized in synaptic junctions bordering transmitter release zones. N. Uchida, Y. Honjo, K.R. Johnson, M.J. Wheelock, and M. Takeichi . The Journal of Cell Biology Volume 135, Number 3, November 1996.)

In the 1990's interest continued to build in the cell adhesion proteins of neurons. I submitted proposals for research funding, but the funding agencies did not want to throw money into the black hole of WSU. If cell-ECM interactions, NCAM family member adhesion, and cadherin-mediated adhesion all occur at synapses, do they share common mechanisms for regulation during synapse modification or are there specific regulatory mechanisms for each type of adhesion? Are there different cadherins in the synapses of different parts of the brain and are they regulated in different ways?

With a small amount of EPSCoR money, students working in my  lab were able to work on cadherin subtype identification by RT/PCR screening, localization of the distribution of cadherins and catenins in the brain, adhesion-dependent tyrosine phosphorylation in cells, and even the role of cadherins in regulating cell death (Wong & Schmidt, submitted).

Another approach is the genetic analysis of behaviorally abnormal animals and the production of genitically altered animals. One student investigated cadherins in Drosophila and another used the long-term memory defective lacking the FYN tyrosine kinase in order to investigate the role of regulation of cadherin function in learning and memory.

John is also interested in constructing neural network models based on biologically realistic model neurons that fit into actual brain anatomical locations. Eventually all folks who are interested in mind are going to have to get together. Books published by Gerald Edelman and Francis Crick have stimulated my interest in consilience within a broad Science of Mind. I think that memory research can be an important unifying theme with such a Science of Mind. I'd still like to talk to a robot before I die.