Dietary folate deficiency is associated with the functional decline of cells, tissues, and organs and the development of acute lymphoblastic leukemias in children. In mice models, leukemogenesis is initiated by Bcr-Abl oncogenic translocations promoted as a result of folate deficiency. Conventionally, cancer is thought to be the result of accumulations of oncogenic mutations over time. Through the application of the Adaptive Oncogenesis model we hypothesize that folate deficiency is likely to reduce the fitness of stem and progenitor cell populations. This reduction in fitness may lead to increase selection for oncogenic mutations that can partially alleviate folate deficiency fitness defects, thereby promoting the initiation of cancers. I tested this hypothesis by mimicking folate deficiency in B-progenitors by using methotrexate (MTX) to target DHFR (dihydrofolate reductase) an enzyme that converts dihydrofolate (i.e. DHF, a folic acid derivative) into tetrahydrofolate (THF) in the folate pathway. I found that in vitro, Bcr-Abl expressing B-progenitors offer partial protection in response to MTX. Furthermore, within a competitive environment, the decline in the fitness of folate deficient B-progenitors promote selection for Bcr-Abl expressing B-progenitors as a result of folate-dependent alterations of the fitness landscape. Expression of the Bcr-Abl oncogene provides a greater competitive advantage compared to control BaF3 Parentals and BaF3 vectors, but only in the presence of methotrexate. These studies establish the development of a cost effective, high-throughput in vitro system to assay for various required components that control folate metabolism and nucleotide synthesis in B-progenitors. Future research will focus on figuring out the mechanisms by which Bcr-Abl B-progenitors are advantageous in a folate deficient environment.
On November 24, 1859, Charles Darwin published The Origin of Species by Means of Natural Selection. The ideas within The Origin, particularly the theory of common descent and the theory of evolution by natural selection, have sparked controversy well into the twenty-first century. This controversy is rooted in the belief that he altered the relationship between religion and science, from one of unity to one of separation. I would like to argue that Darwin did not create a divide between religion and science. Contemporary ideas of a Darwinian divide result from misinterpretations of past conflicts with the Roman Catholic Church, lack of understanding of religious doctrine, fears over certain aspects of Darwin's ideas which some feel conflict with personal religious beliefs, fears over Social Darwinism, and concerns that accepting Darwin's theories promote atheism. In the twentieth century, the belief in a divide between religion and science has come to the forefront due to misinterpretations of Darwin's work and historical misinformation.