Department of Biological Sciences
Wehr Life Sciences, 109
1428 W. Clybourn St.
Milwaukee, WI 53233
Wehr Life Sciences, 506MilwaukeeWI53201United States of America(414) email@example.com
B.S., 2000, Juniata College, Huntingdon, PA
Ph.D., 2006, Yale University, New Haven, CT
Postdoctoral Fellow 2007-2012, University of California- Santa Cruz,
Organisms must respond to their environment
The aim of the research in my lab is to elucidate mechanisms that underlie the ability of organisms to successfully develop and function in the face of environmental challenges. Years of research have given us insight into how organisms develop and function under controlled laboratory settings; however, outside the lab organisms experience a range of environmental challenges, many of which may lead to organismal dysfunction and disease. Very little research has been done on how cellular processes responsible for proper development and function respond to environmental change. Therefore, more exploration is needed to broaden our understanding of what organisms can do in the face of environmental challenges to maintain proper function and also what can go wrong when this does not happen. My research uses C. elegans and mammalian tissue culture to investigate the mechanisms that promote successful development and organismal function in the face of changing environmental conditions, specifically changing temperature.
Buffered or Plastic: Organisms can respond to environmental change in two ways
How an organism responds to changes in the environment is described in two ways. When function or development is not affected by changes in the environment then that organism is buffered to that environmental factor. During buffering the organism employs mechanisms that allow it to respond so that there is no detrimental outcome. However, there is generally a point at which the environmental challenge is so great that function or development begins to be compromised; at this point the organism’s response to the environment is called plastic. The same organisms can have both buffered and plastic outcomes depending on the environmental range. For example, C. elegans maintains fertility between 12°C and 26°C, demonstrating a buffered system, but becomes sterile above 26°C, thus demonstrating plasticity. My lab has two research focuses where we study both of these types of responses.
Buffering of cell fate by synMuv B proteins
A conserved family of transcriptional repressors, the synMuv B family, are important during development in C. elegans to allow for proper cell fate gene expression programs. Establishment and maintenance of cell fate is crucial for organisms because incorrect cell fate leads to detrimental disease states and possible death of an organism. Development of cancer relies on the change in the fate of a differentiated cell that gives it properties that lead to disease. The mechanisms that lead to these changes are a combination of genetic predisposition and environmental challenge. We have shown that synMuv B proteins appear to be especially important in maintaining proper cell fate from thermal challenge. Because homologs of these proteins are highly conserved and are known to play an important role in cancer progression, we are also currently investigate if similar mechanisms underlie the fate changes in cancer cells that sensitize tumors to hyperthermia therapies (i.e. heating of tumors before the use of radiation or chemotherapies). We are using this developmental model of cell fate establishment to investigate how proper gene expression and chromatin structure are maintained during environmental challenge in wildtype organisms, and how these mechanisms are lost in human cancer cells leading potentially to their acquisition of temperature sensitivity. Through the use of these two systems, we will answer fundamental questions as to how organisms that face changing temperatures can continue to develop and thrive.
Losing fertility at high temperature
Sensitivity of the germline to elevated temperature is conserved from worms to humans. For example, loss of fertility in men exposed to high temperature is a known problem in family planning. Additionally increasing temperatures due to global warming could have significant effects on livestock breeding, as many domesticated stocks display decreased fertility during the warm summer months. As a way of investigating the molecular mechanisms that underlie high-temperature sterility and to determine pathways that could be utilized to buffer fertility at high temperature, my lab is studying the natural variation in germline temperature sensitivity in wild-type isolates of C. elegans. The standard C. elegans wild-type strain, N2, demonstrates almost complete sterility at 27°C due mostly to loss of sperm function. Our studies have revealed that wild-type isolates from around the world demonstrate a range of population fertility (from 7%-67%) at 27°C. All strains show some loss of sperm function. However, there are two novel discoveries in our data. 1) There is great variability in the amount of loss of oogenic germline function at high temperatures. Previous work in other species has focused on loss of sperm function and has not shown a disruption in oogenic germline function. 2) There is great variability in the amount that male worms can recover sperm function when moved from high temperatures to lower temperatures. This is in contrast to flies and mammals where there is generally a high rate of recovery of sperm function across all animals when the thermal challenge is removed. Our ongoing studies are using these wild C. elegans strains to determine which aspects of germ cell function are sensitive to temperature. We are investigating if there are differences in gene expression in these different strains, which may underlie their different high-temperature phenotypes. In the long term, we will create recombinant hybrid strains between temperature-sensitive and temperature-insensitive strains. These hybrid strains will enable mapping of loci that are important for buffering fertility at high temperature.
Meghan Fealey (Ph.D. student)
Jerrin Cherian (Ph.D. student)
Franki Compere (Ph.D. student)
Nicholas Sepulveda (Ph.D. student)
Dr. Petrella is currently accepting new Ph.D. students into her lab