Dr. Seeling will use frog developmental and yeast genetic systems to instruct students and to investigate the role of the B56 regulatory subunit of protein phosphatase 2A (PP2A) in Wnt signaling. Her research examines the role of B56 in a pathway that is essential for embryogenesis. Cell-cell signaling pathways transmit signals encoding messages that tell a cell to divide, to differentiate into a particular cell type, or to die. During embryogenesis, cell-cell signaling pathways regulate cell patterning and growth, whereas their inappropriate activation postembryonically can result in tumor formation. Dr. Seeling studies the Wnt signaling pathway, which is regulated by protein phosphorylation. Frequently, phosphorylation activates a protein and also a signaling pathway. Phosphatases reverse phosphorylation, and therefore often inhibit signaling pathways. The project is intellectually important because it focuses on phosphatases, which have been largely overlooked in the study of Wnt signaling. Dr. Seeling previously found that the phosphatase subunit B56alpha inhibits Wnt signaling. Her current research investigates the mechanism by which B56 affects development through its influence on Wnt signaling. The project's research objectives will be accomplished by (1) analyzing the interaction of B56alpha with Wnt pathway protein partners and determining the effects of mutation of these protein interaction domains on B56alpha function, and by (2) characterizing the effects of reduced B56alpha expression on the phosphorylation of three Wnt pathway phosphoproteins that show reduced phosphorylation in the presence of exogenous B56alpha: APC, dvl, and GSK3alpha. This work will help to better understand the regulation of the Wnt pathway in its role in embryo development.
Broader impacts resulting from the proposed activity
The investigator's teaching and research activities will have a strong influence on students at Queens College and elsewhere. The investigator's educational goals include bringing science to individuals at multiple stages of their formal education. An interest in science is best sparked at an early age and then nurtured throughout development. Dr. Seeling's contribution to science education will begin with students of elementary school age, and continue through graduate school. She will recruit underrepresented groups to do research in her lab. The investigator will stimulate students interest in scientific discovery by (1) using frog embryonic development to introduce science to elementary/middle school children at the Queens College School for Mathematics, Science, and Technology, (2) introducing scientific research to high school students, and (3) recruiting individuals from underrepresented groups to carry out independent research projects in her lab. As a faculty member and principal investigator, she will be active in introducing science education to broad age groups, introducing current research ideas to the classroom, and broadening the participation of underrepresented groups in scientific research. Dr. Seeling's study of B56 in Wnt signaling provides a wide range of research projects, from relatively straightforward projects for high school and undergraduate students, such as molecular cloning and yeast two-hybrid assays, to more time-intensive and technically difficult projects for graduate students, including frog embryo microinjections and tissue culture. The research of students at each of these levels will contribute to knowledge of B56's growth regulatory roles and of Wnt pathways' role in development.
This project has produced significant research advances and enhanced the research skills of all of the participants. Our research findings have been presented at seven university campuses, five scientific meetings, and published in two scientific journals. I trained five undergraduate students and four master’s students in laboratory research on this award. The students that have been trained on this award have gone on to graduate school, dental school, a laboratory technician position, or they have used their scientific research background to aid in their business career. This award has also made outreach to local elementary and high schools possible. I have given classroom lessons on frog development to kindergarten and first grade classes at a local elementary school. For these lessons, I brought frogs at various stages development into the classroom for the students to observe. This included eggs that the children could touch, as well as embryos at various developmental stages and adult frogs. In addition, we read a children’s book on frog development, I gave a short presentation on Xenopus laevis frogs, and the children constructed a life cycle diagram of frog development. My presentation described the physical features of Xenopus laevis, showed where Xenopus laevis are from and where they currently live (due to their release into the environment), the type of habitat they experience in the wild and in the lab, and showed the progression of their development from the egg, through metamorphosis, to the adult. The children enjoyed their introduction to life cycles, especially the hands on experience with the frog eggs. Lesson plans to use frogs to study animal life cycles more extensively at this school are under development. The school has twenty-five microscopes available for this lesson plan, and they are very eager to introduce frog life cycles to their science curriculum. From my classroom lessons, I can directly see the need for providing a hands-on science education to an inquisitive and eager student population. I have given several of my laboratory frogs to a local high school that has a special program in agricultural science, and part of this program involves aquaculture and includes internships at local aquariums. The senior animal science class has set up a frog tank and care for the frogs, providing the students additional aquaculture experience. I have provided opportunities to several individuals who may not otherwise have had the opportunity to work in a research lab. Involving undergraduate students in research is an important part of science education, as students who participate in research have a higher retention rate. Therefore, I encourage and promote the involvement of undergraduate students in my lab. I also support the participation of minorities and other underrepresented groups. I have had two female minority M.A. students (one Hispanic and one African American), as well as a male Hispanic high school student. These students have performed well in the lab, as one undergraduate and one M.A. student were each first authors on recent publications. Women are greatly underrepresented in life science faculty positions, and therefore I have nurtured the careers of women by maintaining a 50:50 ratio of female to male trainees. In addition, many of my students have been immigrants, first generation Americans, and/or first-generation college students, and most worked either part-time or full-time to fund their college education. Our laboratory research addresses the function of the Wnt pathway, which is used by cells within animals to communicate with one another. When this pathway is overactive, cells replicate when they should not, resulting in birth defects and cancer. In particular, Wnt pathway hyperactivity is critical in colon tumor formation. We are studying this pathway in frogs, because this system can be used to learn about the pathway more quickly and easily than in other animal systems. We are studying how a type of protein called a phosphatase turns this pathway off. There are several related phosphatases, some that turn the pathway on, and some that turn it off. We are characterizing the role of these phosphatases in the Wnt pathway so that we can determine how to use the phosphatases as a tool to reduce the activity of this pathway to treat cancer. We have learned where and when these phosphatases are expressed in frogs, and we will apply this knowledge to help us understand the function of the phosphatases in humans.
