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Go confidently toward your dreams

June 12, 2000

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    Janis Lochner, Dr. Robert B. Pamplin, Jr., Professor of Science, welcomed entering students and thier parents at Opening Convocation in September.

Presented by Janis E. Lochner, Dr. Robert B. Pamplin, Jr., Professor of Science, at Opening Convocation of the 2000-01 academic year

 

Go confidently in the direction of your dreams! Live the life that you imagined.

 

Perhaps, you recognize these words—the words of Henry David Thoreau. This quotation was appended to an e-mail message that I received this summer. The e-mail was sent by one of my advisees and contained a draft of an essay she had written for her application to medical school. She wrote to ask for a critical reading of the essay. Thoreau’s words were, no doubt, sent to remind me that polishing her essay was another step in working toward her dream—the dream of becoming a physician.

Many faculty at the College work collaboratively with students on research pursuits. In fact, in the Mathematical and Natural Sciences Division, we now have the endowed John S. Rogers Science Research Program to help support collaborative efforts. For example, this past summer, 26 of our students teamed up with faculty to work on research projects.

It is an important time for the student—a time to become actively engaged in doing science rather than simply sitting on the sidelines and studying science. Students grow in interesting ways during the process. Let me tell you about one of my recent experiences.

As a biochemist, I am trained to study the molecular logic of the living state. In recent years, I’ve been most intrigued by the functioning of cells in the nervous system. Specifically, I’ve been curious about the biochemical basis of memory. How are memories encoded? What molecular events and proteins are integral to the process?

I might add that now that I’ve joined the ranks of the middle-aged, I also find myself musing about related, although not quite so uplifting, questions. For example, why has it become increasingly difficult to quickly retrieve some memories?

Over a 100 years ago, neurons were discovered, and synapses, the sites of communication between neurons, were recognized. Ever since, neuro-biologists have struggled to understand the functioning of the nervous system by exploring questions such as how learning is facilitated and how memories are encoded. The rich diversity of communication in the nervous system arises from the regulated secretion of chemical messengers at the synapse.

Synapses are the gateways through which messages are sent and through which lines of communication are established. Interestingly, synapses are not static but can be stably reconfigured. During processes such as long-term memory formation, neuronal architecture is modified.

How does architectural remodeling occur at the molecular level? Results derived from several recent studies suggest that certain proteins facilitate the process by functioning as molecular scalpels. These scalpels are strategically released at the synapse and disrupt existing molecular contacts, thereby allowing growth and accompanying changes in the number and pattern of synaptic connections. We’ve been interested in identifying and studying the proteins that function as molecular scalpels in this remodeling process.

Being a scientist is somewhat like being a detective. Just as a detective seeks to identify potential suspects in a case, a biochemist is looking for a molecule, a protein, to implicate in a specific biological process. The story I have to relate today begins with a suspect. Our quest was to generate compelling evidence that would firmly implicate the suspect in the synaptic remodeling that occurs during long-term memory formation.

What type of evidence do bio-chemists consider compelling? Just as a detective would like to catch a suspect in the act of a crime, ultimately we would like to see our suspect released at the synapse and actively participating in synaptic remodeling. In our work, we began by simply trying to establish a system for visualizing our protein in neuronal cells.

Immediately, we were presented with a challenge. Our protein, like most proteins, is not visible. We couldn’t see our protein even with the most sophisticated microscope.

A creative solution was necessary. We turned to the tools of recombinant DNA technology and, surprisingly enough, to a medusa, a jellyfish that lives in the cold waters of Puget Sound. Why a Northwest jellyfish? Ah, this jellyfish makes a protein with a novel property; the protein fluoresces or glows, thereby permitting visualization by fluorescence microscopy.

Our plan then was to append the gene for this glowing jellyfish protein onto our neuronal gene. We would make a new version of our suspect—a version that glowed, or fluoresced.

High-resolution fluorescence microscopy would be used to image or film the protein in neuronal cells. Clearly, to enact our plan, we needed to recruit students with some diverse talents.

Sam Kuhn ’97 joined our group first. He had already successfully completed a research project with a faculty member on campus, had published his results and was now ready for a new challenge. Sam was a biochemistry major who was conversant with the tools of molecular biology. He began to work out our procedures for joining the jellyfish gene to our neuronal gene.

Mary Kingma ’96, another bio-chemistry major, joined our group after graduating from the College. She worked with us for a year as a research assistant. Mary was charged with caring for our neuronal cells, and she became adept at inducing the cells to take up and express the new chimeric gene. Once we had succeeded in inducing the cells to express our suspect tagged with the glowing jellyfish, we turned our attention to the imaging process.

Bethe Scalettar, a biophysicist and associate professor of our physics department, oversaw this aspect of the project. She recruited Bryan Cutler ’98, a physics major, to assist with the optical imaging—the computational deblurring of images required to enhance resolution and, ultimately, the process of making movies from these images.

Bryan turned out to not only possess the requisite analytical skills for this project but also had great creative flair and wit. Each cell that was imaged was given a name appropriate to the cell’s personality. Likewise, the movies that were made had catchy titles, such as “Hitchhiking the Neuronal Freeways.”

Dan Meliza ’99, a student with interests in biochemistry and biophysics, joined Bryan on this aspect of the project. As Dan worked with Bryan, he began to ask other fundamental questions: How does the cell even know that this protein should be sent to the synapse? What distinguishes proteins that are transported to this site from proteins that take up residence in other areas of the cell? Dan later pursued these questions independently in his honors research project.

Working as a team, we succeeded in making movies that clearly show our suspect being transported to the site where chemical messengers are released. We filmed our suspect being released in response to appropriate stimulatory cues. (For those of you interested in a late-night neuronal flick, many of the movies that we made can be found at either my Web site or Professor Scalettar’s Web site.)

Using these movies, we analyzed the dynamics of protein release and trafficking and published the findings with our four students as coauthors.

The case, however, isn’t closed, and further work on the association between release and synaptic remodeling continues. Moreover, work from other research groups has contributed to the story in significant ways.

For example, one research group made a so-called knock-out mouse—a mouse in which the gene for our suspect protein was ablated. The researchers were able to show that their mice had a selected defect in an electrophysiological process strongly correlated with long-term memory formation. The evidence is mounting that our suspect is, indeed, one of the critical molecular scalpels used in long-term memory formation.

The students who were integral to this work have all graduated and have moved on.

Bryan, our physics major and master filmmaker is now working for a dot-com in the music industry.

Mary, who was so adept at caring for our cells and at inducing them to express the hybrid genes, is now in medical school, and is learning how to skillfully care for patients.

Sam, who couldn’t quite decide if he should follow a medical track or a research track, enrolled in a doctoral program in biomedical engineering at Vanderbilt University. During the past year, he has been involved in a computer-based image-guided surgery project and a project for evaluating surgical glue on bile duct repair. Recently, Dan started a doctoral program in neuroscience at the University of California at Berkeley. He sent an e-mail message to describe his work using fluorescence to study the function of ion channels in neuronal cells.

Socrates stated that true education is the kindling of a flame, not the filling of a vessel. As a faculty member, I delight in seeing the flame kindled. During my 15-plus years at Lewis & Clark, I’ve had considerable time to reflect on just what type of environment promotes the kindling of a flame.

I’ve concluded that one must create an environment where respect is pervasive—a respect for the potential of the student. Asking, indeed sometimes insisting, that the student stretch intellectually, is the primary means of conveying this respect.

Ideally, intellectual challenges should be coupled with the building of a relationship between the faculty member and student—a relationship that supports and guides the student in rising to meet these challenges.

Faculty at Lewis & Clark build relationships with students in an amazing number of ways that extend far beyond the reaches of the classroom.

Today, I’ve given you a glimpse of one such relationship. A group of faculty and students coming together to explore a scientific question—a collaborative endeavor spanning two summers and an academic year. There are, however, many other rich stories of faculty-student interactions.

Some are engrossing tales of faculty who share their expertise not only on campus but by leading overseas study programs. Other stories illustrate how faculty members join forces with students to bring forth grand events, such as the upcoming Environmental Studies Symposium or spring semester’s Gender Studies Symposium and International Affairs Symposium.

As you begin your studies at the College, I would like you to know that we are a faculty who actively engages our students. As my advisee recognized when she sent her essay for a critical reading, we are here to help you move confidently in the direction of your dreams.

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