Potential Mentors for 2021 - 2022

D

Ira Daar

Laboratory of Cell and Developmental Signaling

Research Goals/Purpose:

The mechanisms controlling morphogenetic movements during development involve modifications of cell-cell and cell-matrix adhesion. Abnormal modifications of these adhesion systems are often associated with metastatic progression. Our present focus is on a subset of the Eph family of molecules that are de-regulated in a wide variety of metastatic cancers.

Training Plan:

The student will be taught to use the Xenopus system under my supervision or that of a postdoctoral fellow in the Cancer and Developmental Biology Laboratory. The project will involve completing the functional characterization of the cellular and developmental effects mediated by the intracellular portion of the EphrinB transmembrane Eph ligand. 1) EphrinB mutants will be expressed in developing embryos to determine structural motifs that are important for EphrinB-induced developmental effects. 2) EphrinB will be co-expressed with proteins found to be associated with EphrinB. The ability of these proteins to physically interact with EphrinB will be assayed. The ability to modulate EphrinB-induced developmental effects will also be assessed. 3) The ability of EphrinB to modulate the protein’s activity will also be tested.

Erin Davies

Research Goals/Purpose:

Planarian flatworms are long-lived, regenerative animals that employ different reproductive strategies, including asexual reproduction through fission, sexual reproduction, and parthenogenesis. Sexually and parthenogenically reproducing animals are cross-fertilizing hermaphrodites, and the hermaphroditic reproductive system can undergo degeneration and regeneration in response to amputation, environmental cues, changes in metabolic status, and neuroendocrine signals. However, we understand very little about the mechanisms underlying reversible growth, maturation, and function of the reproductive system, and even less about the molecular basis of reproductive behavior.

Training Plan:

The Davies lab seeks a Werner H. Kirsten Student Intern Program applicant to molecularly characterize degrowth and regeneration of the planarian reproductive system in response to wounding and different types of amputation. The project will involve training in molecular biological techniques, like subcloning, in situ hybridization, immunostaining, light microscopy, image analysis and processing. Long-term behavioral assays to monitor reproductive behavior and fertility will also be employed to investigate how reproduction varies as a function of time post-regeneration. Lessons learned will impact adaptation of germline-mediated transgenesis and gene editing strategies for planarians, and will aid in the creation of an in vitro fertilization platform for planarians.

L

Stephen Lockett

Research Goals/Purpose:

Solid tumors contain a wide variety of cell types that are interacting with their neighbors and more distantly through cytokine signaling. To understand this complexity, it is necessary to label tumors with fluorescence antibodies to identify the scores of different cell types and then to image them microscopically. Next the images must be analyzed to quantify the numbers of each cell type and elucidate the cellular organization of the cells by determining which cell types are neighbors to other cell types. Currently these analyses are being performed in mouse models and changes in the spatial organization of cells, particularly immune cells are being discovered when the mice are treated with experimental therapies. The expertise for understanding these changes in cellular organization of tumors, the capabilities for growing and treating mouse tumors, performing the fluorescence labeling, acquiring the images and analyzing the images with existing algorithms are all in place and underway. However, currently there is a lack of personnel to apply the algorithms to images and to present the quantitative results from analysis in the form of tables, graphs and annotated images.

Training Plan:

II. Description of Training Plan: The WHK intern will fulfill the aforementioned need. In doing so, (s)he will gain knowledge and understanding about tumors at the single cell level, about the process of labeling and acquiring microscope images and about the algorithms for analyzing the images. In terms of the analysis, the intern will learn about the process of segmentation (separation of images into objects (cells) versus background), noise and distortions in images that affect quantification, statistical methods for determining probabilities and significance of results and methods to visually present results. The intern may modify / extend existing algorithms if this is necessary and (s)he appears to have such ability. If the work involves images of human tumors, these images will have been deidentified before the intern has access to them.