Vesicle and Membrane Trafficking Research:
While all membrane proteins are “born” at the same place (the rough endoplasmic reticulum, we’ll call it “the North Shore”), they don’t stay there. Some proteins are destined for California, others may be attracted to the big city lights of New York, and others still may even want to go to the cornfields of Iowa (it’s okay, check my bio)! After they are made in the rough endoplasmic reticulum they are taken to the post office known as the Golgi apparatus where they are then sorted to their specific cellular locations via an elaborate trafficking pathway. As an undergraduate student, I worked with Dr. Mark Stamnes at the University of Iowa on how transport vesicles (the moving vans) bud from this post office and we determined that calcium plays a role in this process.
On the right is the link to the image from Wikipedia, showing the organelles that make up eukaryotic cells.
Because of my wonderful experience as an undergraduate, I decided to pursue graduate school and joined the lab of Dr. Bruce Horazdovsky who was also working on cellular trafficking events. Instead of looking at how proteins moved within the United States (i.e. the cell), we looked at how proteins are imported into the cell, like say how someone immigrates into the U.S. from a foreign country. I worked on a number of projects while getting my Ph.D., all of which were focused on the process of cellular entry known as endocytosis. By far, my favorite projects involved a protein called Alsin. The gene encoding this protein is mutated in a rare juvenile form of amyotrophic lateral sclerosis (ALS2) (and other juvenile neuro-degenerative diseases), the common form of which is known as “Lou Gehrig’s Disease.” While we were able to determine some aspects of this protein’s function and how losing it may cause ALS, there is still much more to learn and I plan to continue these studies with undergraduate students at Gordon.
On the right is a putative model for Alsin function. Loss of this protein may disrupt signaling resulting in decreased neuronal survival.
RNA Processing Research:
After graduate school I decided to study something completely different from what I had learned before. To this end, I joined the lab of Dr. Kristen Lynch (now at the University of Pennsylvania) who works on alternative splicing which is a form of RNA processing. Alternative splicing is a mechanism used by “higher” organisms that generates a much greater diversity in protein output from a smaller genetic input. To produce a protein in a cell, a gene (DNA) is transcribed into RNA in a process that is conceptually similar to printing out a hard copy blueprint from a digital file on your computer’s hard drive. This RNA is then taken to the ribosome whereby it is translated into a protein. Continuing the analogy, the protein is constructed to the specifications of the blueprint (the mRNA). However, before the blueprint is taken to the construction site, it is processed via a number of different mechanisms, one of which is alternative splicing. Let’s say the protein to be made is analogous to a ceiling fan. Alternative splicing would cause the ceiling fan to be modified (say one less blade, the presence of a light, etc.), but it would still be recognizable as the ceiling fan! Back to science… in one extreme example, alternative splicing of the DSCAMgene product in Drosophila (the fruit fly) can encode up to 38,000 different proteins! It is thought that greater than 70% of all genes undergo alternative splicing and that up to 50% of all genetic disease is due to disruptions in this process. Many alternative splicing changes have been shown to be regulated by extracellular stimuli.
In the Lynch lab, we studied alternative splicing in response to activation of the immune system and identified a novel protein that is involved in this process and novel genes that undergo alternative splicing during immune activation. On the right is a model highlighting how cell signaling can induce alternative splicing changes.
Lyme Disease Research:
With colleagues at my previous college, North Park University, I co-led a small research lab composed of undergraduate students. We worked on the most common tick-born disease in the U.S., Lyme disease. This disease is caused by the bacterium Borrelia burgdorferi when it is introduced into a human via a bite of the deer tick Ixodes scapularis. What is very interesting is that while Borrelia burgdorferiis pathogenic (capable of causing disease) it has many cousins that appear unable to definitively cause Lyme disease even though they can be transmitted to humans. The reasons for why this occurs aren’t currently understood. But, because of this discrepancy it is important to know whether ticks in an area harbor the pathogenic Borrelia burgdorferi or one of its non-pathogenic cousins. Our work focused on surveying ticks throughout the greater Chicago area and we found that indeed the pathogenic Borrelia burgdorferi was highly prevalent. I am continuing to work on this bacterium and other infectious agents that can be transmitted by the same tick in collaboration with Dr. Greg Keller. Using a combination of GIS (geographic information system), mammal trapping, and molecular techniques on sites such as forest interiors, forest edges, and my backyard (!), we are determining the role that habitat plays in Lyme disease transmission in the North Shore area.
The figure on the right shows the deer tick vector Ixodes scapularis (left in both real (top) and cuddly form (bottom)), the spirochete bacterium Borrelia burgdorferi (top right), and the most common symptom of Lyme disease, the bull’s eye rash (below right) at the site of the bite (known as erythema migrans). (Images from me or the Public Health Images Library, Center for Disease Control).
Science and Religion Research:
In addition to molecular and cell biology, I am also highly passionate about issues in science and religion. I became a Christian while pursuing my scientific studies and became aware of a tension early on in my career. If evolution is true, then what? Is there only one way to read Genesis? Can’t I just compartmentalize and believe one thing on Sunday and Wednesday and another thing the rest of the week? Or maybe I could think one way in one building and a different way in another? It “worked” for a few years but then it became painfully obvious that it wouldn’t last. I had to tackle the issue head-on. So I began reading. A lot. I’m not sure that I understood all that I was reading but it got me thinking and that is a great, not good thing. Since then, I have developed a love for the study of science and religion and mentoring college students in science and faith. I have written a couple of items for the Jesus Creed blog and Biologos blog and maintain a personal website in the area, but I write cautiously and with humility. There is so much I do not know so I’m hesitant to pronounce this and that. But writing is the best way to synthesize ideas on a matter… and synthesis is necessary for me. All truth is God’s truth. We pursue with intellectual humility, but confidence in our faith.
One reason I love working at Gordon is that my interest in science and religion is shared by all of my wonderful colleagues, which makes for great conversation and also practically enables projects and goals that could not be attained by myself. This is exemplified by the grant that Dr. Craig Story and I received from the Biologos Foundation for a project entitled, “Moving pastors towards scientific literacy.” As part of this grant, I will be writing a book on the pragmatic role of the philosophy of science in Christian discussions on evolution and faith.
On the right are screenshots of my blog and a blurb from NPR about our pastors and science project.