Academics

Gaining an understanding of the mechanism of nuclear transport is fundamental to our comprehension of important cellular events, including regulation of gene expression, response of cells to their environment, and even infection of cells by certain types of viruses, including HIV.  In eukaryotic cells, proteins and RNAs must constantly be transported across the nuclear envelope separating the nucleus from the cytoplasm. The RNA molecules transcribed from genes in the nucleus must be exported to the cytoplasm before they can be translated into the proteins that carry out most cell functions. Specific proteins, synthesized in the cytoplasm, must be imported into the nucleus to carry out such functions as DNA replication, RNA transcription and processing, ribosome assembly, and regulation of nuclear structure (View a video).  These RNAs and proteins cross the nuclear envelope through a large, multi-protein channel termed the nuclear pore complex (NPC) [See figure -Schematic diagram of nuclear pore complex structure. From M. Rout and J Aitchison. (2001) J. Biol. Chem., Vol. 276 (20): 16593-16596. (Full text article here )].

My lab is focused on understanding how the proteins comprising the NPC interact with each other and with soluble “nuclear transport factors” to mediate translocation of proteins and RNA into and out of the nucleus.

The primary method we have used to examine what factors are involved in nuclear transport is to perform genetic screens to identify mutations that affect nuclear transport in the yeast Saccharomyces cerevisiae. By identifying the genes that are mutated in yeast nuclear transport mutants, we can then begin to understand the function performed by the proteins encoded by these genes.  Importantly, nuclear transport occurs by the same mechanism in yeast as it does in other eukaryotic cells, so identifying these transport proteins and their functions in yeast tells us much about how nuclear transport occurs in our own cells. 

Genes that we have identified in our genetic screens encode both NPC proteins and soluble proteins involved in nuclear transport. Students in the lab are continuing to work with these mutants in three different types of projects, each of which uses a different technique to ask how a particular protein might function in nuclear transport.  These projects include:

[ Map of a small region of yeast chromosome X showing NUP82/NLE4 and surrounding genes.  NUP82 encodes a nuclear pore complex protein which is important for efficient nuclear transport. (Chromosome map generated by the Saccharomyces Genome Database: http://yeastgenome.org ) ]

In my research laboratory (like all labs at Colgate) the original, publishable research we perform is carried out by undergraduate students only. This means that students obtain hands-on experience in the lab, working closely with their research advisor to design and implement a research project in which they are intellectually invested and which utilizes laboratory skills they are interested in developing.

My teaching activities integrate my interest in the molecular events that take place inside cells with the resulting cellular activities that regulate the functions and the organization of individual cells, tissues, organs, and organisms.

Molecules, Cells, and Genes (Biol 212) is required of all Biology, Environmental Biology, and Molecular Biology concentrators and provides an in-depth introduction to eukaryotic cell function at the biochemical, macromolecular, and cellular levels. In lecture and lab, students are introduced to and asked to explore such topics as bioenergetics, enzyme kinetics, genes and regulation of gene expression, the cell cycle and the cytoskeleton, intracellular signaling and transport, and organelle structure and function. This class requires students to integrate their understanding of these seemingly diverse topics in order to explore basic cell function and to understand how different cells carry out different activities.

Molecular Analysis (Biol 321) is a “molecular biology methods” course that integrates lectures on advanced molecular biology techniques with labs that utilize these techniques to ask original research questions. In lecture, students read and discuss primary journal articles that utilize modern techniques to investigate problems ranging from how gene expression varies between normal and cancerous cells, to how we can use DNA sequence analysis to determine the evolutionary relatedness of Neanderthals and modern humans, to how recombinant DNA techniques can be used to alter organisms for research, biomedical, and commercial purposes. Biol 321 lab provides the opportunity to use the latest molecular techniques in a semester-long guided research project. Our most recent project used microarrays (DNA chips), quantitative PCR, and other methods to investigate changes in gene expression that occur during the development of an animal from a fertilized egg to a multicellular embryo.

In Developmental Biology (Biol 324) we examine how changes in gene expression and cell-cell interactions influence both the function and the fate of cells in a developing embryo. The progression from single-celled zygote to multicellular organism containing millions of cells requires intricately coordinated molecular events. These events lead to the differentiation of specific cell types that are organized in a specified pattern and carry out specialized activities. Students in Developmental Biology examine such model developmental systems as sea urchins, fruit flies, amphibians, plants, and chicken embryos as they utilize a variety of molecular, microscopic, and microsurgical techniques to examine events occurring during early embryonic development.

Advanced Cellular Biology (Biol 326) is an elective course that utilizes the primary literature and class discussions to investigate cell structure and function. All of the topics covered are areas of intense research in the field of Cell Biology, including mitochondria structure and ATP synthesis, cytoskeletal dynamics, intracellular transport of molecules, regulation of cell cycle progression, and programmed cell death. Students in Biol 326 write increasingly complex papers, climaxing with the synthesis of an in-depth “Current Opinion in Cell Biology” review article at the conclusion of the semester.

Intracellular Transport (Biol 483) is a biology Research Tutorial course in which 6 – 8 undergraduate students undertake an independent research project investigating a novel question focused on understanding how cells move molecules to specific intracellular locations. Students in Biol 483 each have their own project and spend the semester moving rapidly toward being able to design, carry out, and interpret their own experiments utilizing cellular and molecular techniques to investigate cell function.

Cells and Human Development (Core 124) is a Scientific Perspectives course taught as part of Colgate’s Core Curriculum. As a Scientific Perspectives Core course, Cells and Human Development uses the field of human fertilization and early development to explore how scientists investigate new questions, analyze qualitative and quantitative data, and communicate the results and significance of their investigations. In addition, discussions focusing on assisted reproduction (in vitro fertilization), somatic cell nuclear transfer (“cloning”), stem cell research, and gene therapy allow us to investigate the potential impact scientific findings and technological advances have on society.

All of these courses, from the first-year seminar to the research tutorial, emphasize student comprehension of the process by which scientific information is obtained. This means that we spend considerable time discussing not only what we understand about specific aspects of biology, but also how scientists investigate the functioning of molecules, cells, and organisms. All courses require reading of the primary scientific literature, design and/or execution of an original research experiment, and reporting on the results of the experiment in either the format of a primary journal article or as an oral report.  It is my goal to have students leave these courses not just having learned some new ideas about a particular area of biology, but also having taken a significant step toward “thinking like a biologist” and asking new questions about the field they have just spent a semester examining.

Research students from my lab have gone on the graduate school at:

• Stanford University
• University of California – Berkeley
• Yale University
• Vanderbilt University
• Northwestern University
• Duke University
• Columbia University
• Johns Hopkins University
• University of Pennsylvania
• Dartmouth University
• Cornell University
• Brandeis University
• Mayo Graduate School
• Temple University
• Indiana University
• University of California – Santa Cruz
• University of Toronto

Some medical schools my research students have enrolled in are:

• Johns Hopkins
• Washington University
• University of Michigan
• University of Rochester
• Jefferson Medical College
• Vanderbilt University I
• ndiana University
• St. Louis University
• SUNY Upstate

Undergraduate research students have also gone on to find employment in many areas, from biomedical research to pharmaceutical development to education to finance. A few of the employers with whom recent graduates have become employed are:

• Harvard University
• National Institutes of Health
• UCLA
• Roswell Cancer Institute
• Genuity Capital Markets
• University of Chicago
• Pasteur-Aventis Pharmaceuticals
• Sloan-Kettering Medical Center
• Cornell University
• University of Rochester
• Mt. Sinai Hospitals
• University of Southern California

Selected Student Research Presentations:

(* Indicates Colgate undergraduate student co-author)

Pettit M*, Kokanovich K*, Yewdell WT*, Barber M*, Hussain N*, Damuth EK*, Belanger KD. (2007) “The nuclear export of the Swi6 transcription factor is regulated by at least two karyopherins in S. cerevisiae.” American Society for Cell Biology annual meeting, Washington, DC.

Belanger KD, Tkachev D*, Belanger KG, Geier SJ, Aurora R. (2007) “The karyopherin Sxm1/Kap108 regulates gene expression under normal and oxidative stress conditions in S. cerevisiae.” American Society for Cell Biology annual meeting, Washington, DC.

Belanger KD, Tkachev D*, Geier SA, Belanger KG, Aurora RA. (2007) “Examination of the role of nuclear transport in the response to oxidative stress in S. cerevisiae.” Systems Biology Workshop, St. Louis.

Harper NC*, Al-Greene N*, Basrai M, Belanger KD. (2005) “NUP1 functionally interacts with components of the spindle pole body and mitotic exit network.” American Society for Cell Biology annual meeting, San Francisco, CA.

Barber M*, Hussain N*, Damuth E*, Belanger KD. (2005) “Identification of a putative nuclear export signal in SWI6.” American Society for Cell Biology annual meeting, San Francisco, CA.

Belanger KD, Perazone T*, Yelton A*, Belanger KG. (2005) “Examination of the role of regulated nuclear transport in the response to oxidative stress in S. cerevisiae.” NSF-FIBR workshop on Systems Biology. Washington University, St. Louis, MO.

MacDonald K*, Ott C*, Davis LI, Belanger KD. (2004) “Nuclear pore complex function is influenced by glycosylation in Saccharomyces cerevisiae.” Yeast Genetics Meeting, Seattle, WA.

Belanger KD, Simmons LA*, Lichten LB*, Roth JK*, VanderPloeg KA*. (2003) “Msn5/Kap142-mediated nuclear import utilizes a subset of nucleoporins distinct from the Nups required for Msn5-mediated export.” American Society for Cell Biology Annual Meeting, San Francisco, CA.

Belanger KD, Simmons LA*, VanderPloeg KA*, Roth JK*, Lichten LB* (2003) “Distinct sets of nucleoporins mediate Msn5-mediated import and export through the nuclear pore complex.” Yeast Cell Biology, CSHL, NY.

Belanger KD, Davis LI, Simmons LA* (2002) “Identification of a functional and physical interaction between the nucleoporin Nup1 and the Mex67/Mtr2 export pathway.” Dynamic Organization of the Nucleus, Cold Spring Harbor, NY.

Roth JK*, Lichten LB*, and Belanger KD (2002) “The karyopherin Msn5 is mislocalized in a mutant of the nucleoporin Nup82.” Dynamic Organization of the Nucleus, Cold Spring Harbor, NY.