DR CHRISTINA FANG

Country of Origin: Taiwan
Subject: Genetics
Matriculation Year: 2011

Introduction of Ph.D. work

I pursued my Ph.D. in the Department of Genetics at the University of Cambridge. My work sought to dissect and delineate the signalling dynamics of Wnt and Notch signalling pathways in the regulation of homeostasis and regeneration in the Drosophila melanogaster (fruit fly) midgut. Wingless (Wg)/Wnt signalling is the primary driving force in the maintenance of intestinal homeostasis, and dysregulations in the Wnt pathway can lead to the onset of colorectal cancers. However, the organization and function of Wg/Wnt signalling remain poorly understood. Due to their similarities to the mammalian system, and the advantages they offer as a model genetic system, studies using the adult Drosophila midgut may provide insight into the elusive role of Wg/Wnt signalling in tissue homeostasis and regeneration.

My Ph.D. research characterised the pattern of expression of wg and of its effector Armadillo in the adult Drosophila midgut and correlated them with the response of midgut cells. I revealed that in normal homeostasis, there is a gradient of Wg signalling in the intestinal stem cell (ISC) and the undifferentiated progenitor cell (enteroblast) across the midgut, with a gradient maxima at the midgut/hindgut boundary. This gradient resulted from a combination of two sources of Wg: a fixed source at the boundary and a second source in the ISCs and enteroblasts themselves. Furthermore, I observed that Wg expression and signalling in the epithelium are stochastic and change over time. Using gain and loss of function, I revealed a requirement for the global response to Wg signalling in the maintenance of midgut morphology. Finally, I analysed the interaction between Wg and Notch signalling in the maintenance and proliferation of ISCs.

Altogether, this study helps clarify the source of Wg signals, and raises novel points about the function of Wg signalling in Drosophila midgut homeostasis and regeneration.

Where I did my undergraduate degree

I did my undergraduate degree at the National Tsing Hua University in Taiwan, where I majored in Life Sciences.

Where I went subsequently

I am currently a postdoctoral fellow in the laboratory of Dr. Edward Giniger at the National Institutes of Health in the United States. My current project has established a 3D live imaging method that enabled the discovery of an unprecedented model of neuronal growth which, in conjunction with a wide variety of pharmacological and biophysical methods, has allowed me to design fast frame-rate and high-resolution studies of live, single neuronal development. Using these techniques, I am studying the components of the Abelson signalling pathway that are responsible for neuronal axon growth.