David Lindsey, Professor of Biology and Department Chair

EDUCATION
Ph.D. 1992 University of Texas

COURSES
BIOL 142 - General Biology
BIOL 383 - Cell Biology III
BIOL 430/530 - Molecular Biological Techniques
BIOL 445 - Advanced Microbiology

CONTACT INFORMATION
509-527-2602
david.lindsey@wallawalla.edu

RESEARCH INTERESTS

The transformation of a fertilized egg to a complex multicellular organism depends on a variety of mechanisms that control cell-cell communication and changes in gene expression. The selective destruction of specific proteins is one of the important mechanisms that control this developmental process. Many proteins are selectively degraded by the ubiquitin-dependent proteolytic pathway. In this pathway, linkage of a protein to ubiquitin targets the protein for degradation by the proteasome. Defects in this pathway have been implicated in a wide range of human disorders including tumor formation and neurodegenerative diseases.

We are interested in understanding the role of ubiquitin-dependent proteolytic pathways in multicellular development. We use the social amoebae Dictyostelium discoideum as a model system. It is a simple and elegant system to study fundamental developmental processes that are used by higher systems including growth-to-differentiation transitions, directed cell movement, cell-type determination, and formation of structures with specific size and shape.

Dictyostelium normally exists as solitary cells that proliferate by cell division while feeding on bacteria in soil and decaying leaves. When stressed by starvation, these amoebae stop dividing and enter a developmental program that results in the formation of a multicellular fruiting body. The cells first aggregate into a mound which then elongates to form a slug that can migrate to a suitable location for fruiting body formation. Cells specified to become stalk cells, the prestalk cells, occupy the tip of the slug; the posterior region of the slug contains mostly prespore cells. Eventually, coordinated cell movements and additional differentiation events result in a fruiting body consisting of a mass of spore cells supported on a column of stalk cells.

We have identified two enzymes that appear to function in ubiquitin-dependent proteolytic pathways and are required for Dictyostelium development: UbpA and RbrA. UbpA is a functional homolog of the yeast Ubp14 and human isopeptidase T, enzymes which appear to function in the disassembly of free ubiquitin chains following their use as tags for protein degradation. It is likely that these enzymes facilitate ubiquitin dependent proteolysis by preventing free ubiquitin chains from competing for substrate binding sites on the proteasome. Control of cellular ubiquitin chain levels by UbpA may provide a mechanism for modulating the rates of protein degradation by the proteasome during changing developmental conditions. We are currently investigating the role of UbpA at the growth-development transition by analyzing defects found in ubpA-deficient cells. Results from this work may elucidate molecular mechanisms that underlie the conversion of stem cells to differentiating cells.

RbrA is a putative ubiquitin ligase that is required for cell-type proportioning and pattern formation. rbrA-deficient cells form slugs that are unable to phototax or develop into fruiting bodies. RbrA is highly similar to ariadne-like ubiquitin ligases, which are members of the RBR family. RBR family members are widespread in eukaryotes and include parkin, a gene implicated in Parkinson's disease. To delineate RbrA-dependent pathways, we are using genetic, molecular, and biochemical approaches to identify proteins that interact with RbrA.

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Last update on October 31, 2013