Summer Research 2014
Upcoming Summer Research
We are excited to announce we will be hosting 7 different visiting scientists. It’s going to be a busy summer in the NXR!
But don’t forget about visiting year-round. If you have the projects, we have the frogs and the resources!
|Artur Llobet (MBL Research Award)
Bellvitge Biomedical Research Institute
Rewiring of Sensory Inputs in the Xenopus Brain
Some amphibians are capable to recover the functionality of their sensory inputs after suffering traumatic injuries. Following a lesion, their neuronal circuits can be repaired and synaptic connections restored to normal function. Using transgenic Xenopus tadpoles, I aim to understand how synaptic connections established by olfactory sensory neurons recover the capacity to transmit information after an injury. My experimental methods are based in correlative studies of morphology and in vivo measurements of intracellular calcium changes. Results will shed light on mechanisms controlling formation and maturation of synapses during rewiring of neuronal networks.
|David Furlow (MBL Research Award)
Metamorphosis in frogs and toads, as well as in certain insects and crustaceans, represents the most dramatic effect of any hormone in nature. We are studying the molecular mechanisms underlying how thyroid hormone, which also critically regulates brain development and overall metabolism in humans, induces a wide variety of tissue changes that turn the purely aquatic tadpole into the adult frog. These remarkable changes are mediated by specific thyroid hormone receptor subtypes that act as ligand regulated transcription factors. However, the precise role of each receptor subtype in tissue specific and developmental stage specific responses to the hormone are unclear. We are applying emerging powerful genetic approaches in Xenopus laevis and Xenopus tropicalis available at the Xenopus National Resource at MBL to reduce the expression of each receptor subtype, and test their importance in specific pathways during early development and thyroid hormone dependent metamorphosis. These studies will contribute to our understanding of tissue specific actions of hormones in a developmental context, using this highly evolutionarily conserved endocrine signaling system.Another important aspect of our work is determining the effect of environmental chemicals on proper thyroid hormone signaling in vertebrate development. We are further applying the available genetic technologies now available in the organism to produce tadpoles that express an easily measurable, hormone responsive reporter gene. This will allow us to detect proper temporal and spatial thyroid hormone action in vivo, in response to both endogenous hormones and potential environmental contaminants. Thus, our research is focused on answering basic questions regarding thyroid hormone’s action during development, with clear biomedical and environmental toxicology applications.
Bob Rose (MBL Research Award)
North Carolina State University
Transcriptional regulation of pancreas development
My lab at NCState University studies interactions among transcription factors that regulate tissue-specific gene expression using protein crystallography, and biophysical and cell-based assays. We focus on pancreas transcription as a model system. Pancreas development has been intently studied to develop treatments for diabetes and pancreatic cancer. The collaboration with NXR and Marko Horb will allow us to merge structural questions with genetic and developmental approaches in Xenopus laevis.
Transcriptional regulation of pancreas development is conserved between Xenopus and humans. Two transcription factors, Pdx1 and Ptf1a, possess properties of master regulators of pancreas development: both are required for differentiation of the exocrine and endocrine cell lineages of the pancreas. The potency of these factors is demonstrated by their capacity to transdifferentiate liver to pancreas in Xenopus. Pdx1 and Ptf1a regulate hundreds of genes during pancreas development, and their activity is restricted by interactions with other factors.
During the summer we will be characterizing the regulatory role of the Pdx1-Pbx1 complex. We propose that cooperative interactions between Pdx1 and the transcription factor Pbx1 regulate cell proliferation, a critical aspect of development. In addition we will be applying Crispr technology to try to isolate and characterize transcriptional complexes on enhancers during pancreas development. These studies will further our efforts to identify enhancer complexes for X-ray crystallographic studies.
|Reyna Martinez(Grass Fellow)
State University of New York
The role of intermediate filament proteins in neural degeneration and regeneration
The expression of intermediate filament proteins (IFPs) in glial cells has been implicated in the inability of some vertebrates to regenerate the central nervous system. Taking advantage of the ability of Xenopus laevis to regenerate the retina, I will use the XOPNTR transgenic line, a model of rod degeneration and regeneration, to determine the role of IFPs in these two processes. Specifically, I will investigate if the IFPs glial fibrillary acidic protein (GFAP) and Vimentin are important regulators of retinal degeneration and the ability of the Xenopus retina to regenerate. I will be using transgenesis to return GFAP to the genome of XOPNTR transgenics and TALENs to eliminate Vimentin. The results of this study will determine if upregulation of GFAP and Vimentin IFPs is required for Müller cell reactivity, retinal degeneration and restricting the regenerative capacity of the retina.
|Aaron and Christina Zorn (Research hotel visiting scientists)
Cincinnati Children’s Research Foundation
(Research hotel visiting scientist)
University of Connecticut
The voltage sensitive phosphatase (VSP) was discovered ten years ago in C. intestinalis, and though it is widely conserved among vertebrates and has been the subject of many studies, to date a physiological role for it has remained elusive. This intriguing protein has the voltage sensor domain of an ion channel coupled to a cytoplasmic phosphoinositide phosphatase, with membrane depolarization activating its enzymatic activity. Our initial characterization of the Xenopus VSPs alluded to a possible role in sperm-egg fusion, and preliminary studies also indicted a possible role in early development as well. My studies conducted at the NXR this summer aim to further this second line of inquiry by use of genetic manipulation of VSP expression in the early embryo.
The NXR will have space available for summer researchers as well as facilities to maintain frog lines during the summer and frogs for sale to use.
If interested in conducting research during the summer or during the rest of the year, please contact Xenopus@mbl.edu for more information.