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Kinase dependent mechanisms regulating stem cell populations during embryogenesis.

Principal Investigator: Dr. Aaron Putzke

We are interested in how cells communicate with each other during embryogenesis to determine cellular identity, timing of cell divisions and spatial relationships that ultimately form different tissues and organs. Specifically, we focus on the influence of cell adhesion mechanisms during embryogenesis, and how cell-cell contacts affect tissue specification. To investigate these phenomena we use two model organisms: the nematode, Caenorhabditis elegans and the zebrafish, Danio rerio.

We have cloned a non-receptor tyrosine kinase, called Fer, and found that it localizes to, and stabilizes, cadherin-mediated adhesion complexes at the plasma membrane. During early embryonic development in C. elegans, the consequences of losing cell-cell contacts, via loss of Fer (called FRK-1 in C. elegans) function, include the loss of cellular differentiation in the "skin" cells (called the hypodermis) and inhibition of embryonic enclosure.

A secondary effect of losing FRK-1 function is that we observe extra cell numbers in multiple tissue types, the specification of which is driven by a signaling mechanism known as the Wnt pathway. We are investigating the hypothesis that FRK-1 function not only stabilizes cell-cell contacts, but also prevents over-activation of the Wnt pathway.

Additionally, we are interested in examining the similarities between Fer homologues in vertebrates and invertebrates. Fer belongs to a non-receptor tyrosine kinase family called the Fes/Fps family. This is of particular interest because Fer kinase expression has been found to be altered in a variety of human cancers. By investigating the function in Fer/FRK-1 in both model organisms we aim to uncover novel protein interactions that may ultimately lead to advancements in our knowledge of mechanisms in development and cancer.

Students in our lab learn how to generate hypotheses, design experiments using a wide variety of molecular, genetic and embryological techniques, and draw conclusions from collected data. The projects in the lab branch into two categories.

1) C. elegans: We are analyzing the relationship of FRK-1 to the Wnt pathway in affected tissues when FRK-1 function is lost.

2) Danio rerio: We have identified the Fer/FRK-1 homologue in zebrafish and are performing gene expression analysis to determine when and where the gene is expressed during embryonic development.

The Putzke lab includes a dynamic mix of hard-working students, curious to investigate how embryos develop from one cell into a functioning embryo. If uncovering cellular signaling pathways using model organisms sounds exciting to you come join us!

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