DPY-26 and MIX-1: An Investigation of Dosage Compensation and Chromosome Condensation in C.elegans

Lindsay Dick

Research Advisor:  Dr. Jason Lieb

Research Mentor: Dr. Sevinc Ercan

In many organisms, including humans, males and females possess different complements of sex chromosomes; this results in unequal expression of X-linked genes between sexes. Via the Dosage Compensation Complex (DCC), C. elegans XX hermaphrodites halve transcription levels across both X chromosomes to match the expression from XO males. We developed antibodies against two members of this complex: MIX-1 and DPY-26. Both of these proteins are also homologous to members of the condensin complex, which aids in chromosome condensation and segregation. Using chromatin immunoprecipitation followed by hybridization to whole-genome microarrays (ChIP-chip), we mapped the binding locations of MIX-1 and DPY-26. Results obtained from these experiments support previous theories of a recruitment-and-spreading mechanism for DCC function. Currently, we are seeking to illuminate the functions of MIX-1 and DPY-26 within the context of the condensin complex. These data aid in understanding how transcriptional activity is fine-tuned at individual loci through larger chromosomal processes.

The Functional and Physical Relationships Between Two DNA Repair Proteins in Drosophila melanogaster

Lena Hyatt

Research Advisor: Dr. Jeff Sekelsky
Research Mentor: Sabrina Andersen

Bloom Syndrome is a rare disorder characterized by immunodeficiency, sterility, short stature, and a predisposition to many types of cancer.  The disorder is caused by a mutation in BLM, which encodes a DNA helicase. BLM is thought to interact with RAD51, a strand invasion protein, to facilitate the homologous repair of DNA double-strand breaks (DSB). We hope to discern some aspects of this interaction by examining mitotic crossovers in irradiated Drosophila melanogaster with mutated mus309 (DmBLM) and spn-A (DmRAD51), and by yeast-two hybrid assays to characterize physical interactions in vitro. Previous studies have shown that DmBLM mutants have increased mitotic crossovers (CO) when repairing DSB, an indication of aberrant repair. We found that flies with both mutated mus309 and spn-A have reduced CO rates compared to mus309 mutants alone. These results confirm that SPN-A acts upstream of BLM in the DSB repair pathway. .

The Role of Notch Signaling in Endothelial Precursor Cell Formation

Christina Lee

Research Advisor:  Dr. Suk-Won Jin
Biology Sponsor: Dr. Victoria Bautch

Notch signaling is an evolutionarily conserved, intercellular signaling pathway with an essential role in a variety of developmental processes, including cell-fate determination, differentiation, and proliferation.  My project investigates the function of Notch signaling in the specification of the hematopoietic (blood) and endothelial lineages in early embryonic development.  In treating zebrafish (Danio rerio) embryos with DAPT, a chemical antagonist of Notch activity, we found a significant increase in the number of endothelial cells (ECs) and a decrease in hematopoietic cells (HCs).  Confocal and flow cytometry analyses confirm our hypothesis that Notch signaling promotes blood formation and suppresses EC formation.  To test whether this pathway may function as a cell-fate switch between the two lineages, we plan to inhibit Notch in bloodless mutants, which lack primitive hematopoietic cells.  These studies will provide further understanding of how the specification and differentiation of different progenitor populations in the nascent mesoderm is regulated.

Combined Effect of Two Chemicals, Fluoride and Alendronate Bisphosphonate, on the Vertebrae Structure of Mice

Laura Panos

Research Advisor:  Dr. Eric Everett
Biology Sponsor: Dr. Corbin Jones

 

Bones go through a remodeling process where cells called osteoblasts and osteoclasts work to maintain bone structure.  There are two chemicals, fluoride and bisphosphonate, that have been used to treat bone disorder patients.  Fluoride suppresses bone growth, while bisphosphonate suppresses bone resorption.  It was hypothesized that mice given both fluoride and bisphosphonate would show increases in trabecular bone mass, measured in terms of bone mineral density, as well as trabecular thickness and number.  Trabecular bone is the spongy bone lining the bone cavity with a high surface area.  Eight strains of young mice with known fluoride tolerances were given fluoride drinking water and a weekly injection of bisphosphonate for three weeks.  A Micro tomography scanner captured X-ray images of the vertebrae and converted them into 3D shapes for analysis.  The results indicate that fluoride and bisphosphonate affect mammalian bones and suggest their individual responses are due to genetic differences.

Reproductive Character Displacement by Male Aggregation Behavior in Spadefoot Toads

Alyssa Stewart

Research Advisor:  Dr. Karin Pfennig

The hybrid offspring of two closely-related species are typically less fit than either of the parental species, making interbreeding disadvantageous.  One process that facilitates same-species mating is reproductive character displacement, in which species evolve divergent behaviors to minimize risk of interbreeding.  This may be the case with two species of spadefoot toads (Spea multiplicata and S. bombifrons) in regions where they coexist and I will test this possibility by observing aggregation behavior in simulated breeding pools.  I hypothesize that males from regions where both species exist are more likely to distinguish between the two species calls and will preferentially associate with their own species, thereby reducing the likelihood of interbreeding.  Conversely, males that come from regions where coexistence does not occur will be less likely to discriminate between the calls.  Such results would suggest that male behavior plays a critical role in reproductive isolation between S. multiplicata and S. bombifrons.