About Us | Events | Contact Us

People of Science House

Margery Smelkinson - Biological Scientist

Background

The first time I remember being really excited about science was when I first learned about outer space.  I was intrigued by the concept of the Big Bang as a way of explaining how the universe came into being.  Even less conceptual, I was simply amazed that there were eight other planets (seven now since Pluto is no longer categorized as being a “planet"), big and small, sharing our sun.  It was also the first time I had given much thought to what a star is and that our sun is just another star.   And of course my mind was blown that those billions of stars we see may potentially have billions of planets revolving around them and that with the right size, gravity, and molecular components, there could be a planet out there like ours that provides a habitable atmosphere that currently has or is suitable for life.  It’s a bit abstract to think about, especially for a third grader which is when I was first introduced to this topic, but from then on, I have always been intrigued by space exploration. 

"My mind was blown that those billions of stars we see may potentially have billions of planets revolving around them."

When I started college, I was an astronomy major.  However, I was soon introduced to developmental biology where I found the study of cellular processes and how cells communicate with each other fascinating.  During college and graduate school, I investigated ways in which two highly conserved signal transduction pathways crucial for growth and development, Wingless/Wnt and Hedgehog, are properly regulated.  I am now interested in how viruses alter and exploit these types of cellular processes to their own advantage.


Current Work

Currently, I am using the fruit fly, Drosophila melanogaster, as a model organism to study cellular targets of viral proteins.  Viruses typically have very few genes that can be transcribed into proteins (sometimes even less than ten).  Despite the small genome sizes, devastating effects can occur during times of outbreak resulting in epidemics and large-scale pandemics.  To ensure viral replication and maturation, viruses must use their small amount of genes extremely efficiently.  Some viral proteins function at least partially by interacting with host cellular components in ways that are beneficial to the virus but may be detrimental to the host.  We would like to identify cellular targets of genes from various viruses and determine if they are associated with virulence.  Once we isolate a cellular target(s) of a viral protein, we can then screen for inhibitors that block this interaction that could be developed in mammalian systems to combat infection.  It is probable that blocking the function of even one gene could severely handicap the viruses from maturing and/or spreading.

"I found the study of cellular processes and how cells communicate with each other fascinating"

Why do this study in flies?  Due to the high conservation of disease genes (genes that, when mutated, cause disease) between flies and humans, Drosophila can serve as a powerful yet inexpensive host model to study these interactions.  Drosophila offers several important advantages over mammalian systems as a model multicellular organism to study host/pathogen interactions including: 1) a short generation time (10 days), 2) the ability to screen through large numbers of progeny (105-106 individuals), 3) well developed genetic tools for loss and gain-of-function studies and well characterized phenotypes associated with genetic mutations, 4) easy analysis of dosage sensitivity of phenotypes which provides a highly sensitive assay system for gene function, and 5) using a multicellular organism (compared to a mammalian tissue culture system) would allow for the observation of cell non-autonamous effects (one cell causing an effect on another cell).  Therefore, we can first use the fruit fly to quickly screen viral genes for interactions with host targets and then follow up those studies in mammalian systems.


Mentors

The mentor that has taught me the most about science exploration was my advisor during graduate school, Dr. Dan Kalderon.  Dan taught me how to think like a scientist which is to focus on the questions I want to explore and develop appropriate and feasible experiments for the investigation.  For almost 6 years, I worked in his lab where he treated me like a colleague rather than a student.  We had many long discussions about my data that would leave me excited to perform the next set of experiments.  By learning under him, I was also able to develop a critical eye which is extremely important when analyzing scientific data.  For my own research, this has made me very careful about how I choose experiments and the corresponding controls to carry out that would be the most relevant for the question at hand. Conducting research in this manner will always accelerate the evolution of the hypothesis.

Another mentor who was very important in my scientific career is the post-doc I trained under as an undergraduate, Frieda Reichsman.  This was my first lab experience and Frieda showed me the ropes of lab life and taught me what constitutes the experimental procedure.  In addition to making me feel comfortable in the lab, she helped me form my ideas and figure out ways to test them. When I made mistakes, and believe me, I made many and still do, Frieda assured me that that’s part of science and can sometimes even lead to big discoveries.

 

Background

headshot
Occupation:
Post-doc at the University of California, San Diego
Education:
Ph.D. in Biological Sciences, Columbia University

M.A. in Biological Sciences, Columbia University

B.S. (Honors) in Biochemistry and Molecular Biology, University of Massachusetts
Research:
Postdoctoral research in the lab of Ethan Bier, University of California, San Diego, (present work)

Graduate research in the lab of Dan Kalderon, Columbia University

Undergraduate research in the lab of Susan Cumberledge, University of Massachusetts

 

Awards and Recognition

Awards

  • Peter Sajovic Memorial Prize
    (Awarded to a graduate student doing outstanding work in biology)

    Inducted into Phi Beta Kappa

    Golden Key National Honor Society, National Society of Collegiate Scholars, and accepted into the Junior Fellows Program (research scholarship)

Published Papers

  • Smelkinson MG, Zhou Q, Kalderon D.  Regulation of Ci-SCFSlimb Binding, Ci Proteolysis, and Hedgehog Pathway Activity by Ci Phosphorylation. Dev. Cell, 2007;13: 481.

    Smelkinson MG, Kalderon D. Processing of the Drosophila Hedgehog Signaling Effector Ci-155 to the Repressor Ci-75 Is Mediated by Direct Binding to the SCF component Slimb. Curr Biol. 2006;16:110.
  • Presentations

    • "Partial proteolysis of Cubitus interruptus is mediated by a direct interaction with Slimb",
      Poster presentation at the 47th Annual Drosophila Research Conference, Houston, TX, 2006.

      "How Ci gets Slimb", Columbia University Biological Sciences Department Student Seminar, New York, NY, 2005.
    • "Slimb dependent partial proteolysis of Slimb", Columbia University Biological Sciences Departmental Retreat, New Paltz, NY, 2004.

      "Maturation of an active Wnt signal:  glycosylation and formation of disulfide-linked oligomers", Poster presentation at the Wnt Meeting, New York, NY, 2001.

      "Oligomerization of the Drosophila protein, Wingless", Poster presentation at the Seventh Annual Undergraduate Research Conference, Sturbridge, MA, 2001.