SCC Biology Research Symposium, Fall 2013
The Scottsdale Community College Department of Life Sciences held its semester symposium for fall 2013 on Thursday, December 5. The symposium included two plenary speakers from my lab (Joe Juliano and Scott Bickel), an invited talk by Matthew Ykema, who works in Dr. Jorge Reyes del Valle's lab at ASU, presentations from three undergraduate research teams in my lab (talks by Andrew Nemecek and Sabrina Jones on Mono Crates Pikas, Kody Holmes on dispersal in artificial metapopulations of Tribolium, and a poster by Kirsten Karr and David Ung on the evolutionary ecology of cancer) and four presentations by students in our Introduction to Biological Research class. Here are abstracts from select presentations (pdf format available here).
Plenary 1: Microglia Motility in the Context of a PDGF Induced Glioblastoma
Joe Juliano, Orlando Gil, Andrea Hawkins-Daarud, Russ Rockne, Jill Gallaher, Alexander Anderson, Peter Canoll, Kristin Swanson
Abstract. Glioblastoma multiforme (GBM) is the most aggressive, and most common, primary brain tumor. Median survival remains around approximately 14 months after initial diagnosis. Recent studies have shown that up to 30% of the composition of glioblastoma is composed of microglia and macrophages, which are part of the CNS innate immune system. Through mechanisms that are still not well understood, and contrary to normal immune function, these tumor associated microglia-and-macrophages (TAMS) are hijacked by glioma cells to aid the progression and invasiveness of glioblastoma. To investigate properties of TAMS in the context of glioblastoma, we studied TAMS migration in a PDGF-driven rat model of glioma that resembles human glioblastoma. We differentially labeled glioma and microglial cells using fluorescent tags and mapped their movement using time-lapse microscopy. Here we show that microglia tend to localize within the tumor border, and microglial cells in the tumor move with greater motility than do those outside the tumor environment. The majority of microglia movement was characterized by a power law distribution with a characteristic exponent that decreases outside the tumor region. This result indicates that microglia travel at greater speeds within the tumor region than outside of it. This study highlights the importance of microenvironmental factors as modulators of microglia behavior and the need to further characterize how the tumor may benefit from surrounding microglia motility.
Plenary 2: Mutational contingency dominates clonal selection in evolving tumors
Scott Bickel, Joe Juliano, and John D. Nagy
Abstract. Tumors are often viewed as highly phenotypically diverse entities composed of multiple competing clonal lineages. Recently published literature suggests that several key characteristics or ``hallmarks" are commonly observed in most tumors (Hannahan and Weinberg, 2011). Genomic instability fuels the accumulation of clonal diversity; however, it is not well understood how all tumor hallmarks evolve, including one of the most prominent---uncontrolled angiogenesis (the production of new blood vessels from pre-existing vasculature). Here we continue analysis of a stochastic simulation of cancer that models clonal selection acting on two critical phenotypic traits conferring malignancy to tumors---proliferation and angiogenesis effort. Previous investigations of this model have shown that uncontrolled angiogenesis can be favored or disfavored, in terms of inclusive fitness to the clonal lineage, depending on the proliferation phenotype of the clone. Mathematical analysis of this two-dimensional strategy space, using adaptive dynamics (which assumes tiny incremental steps in phenotypic mutations), shows that all tumors should evolve towards vascular hypoplasia and tumor necrosis. However, this endpoint is rarely observed in stochastic simulations. Instead, most tumors continue to sustain angiogenic signaling and grow to lethality. Here we show that clonal selection on these two key phenotypes in cancer is dominated by mutational contingency, specifically the order and timing of mutations. Simulations beginning with same initial clonal lineage result in several different outcomes determined solely by mutational history within the tumor. Therefore, the deterministic evolutionary endpoint has little consequence since it is rarely realized. This result stresses the importance of information about a tumor's genetic history needed to predict the disease's clinical behavior in individual patients. A more complete view of a individual tumor's natural history may allow for possible interventions that can force tumors towards the evolutionary endpoint---i.e. evolutionary suicide---or may give more insight into the evolutionary consequences of therapies currently used or in development.
Invited talk: Effects of Cholesterol Depletion on the Infection Cycle of Measles Virus
Matthew Ykema and Jorge Reyes del Valle
Abstract. Measles is a single stranded RNA virus that was a major public health issue before the development of a vaccine in the 1970’s. The infection cycle involves the formation of syncytia, clusters of cells that produce high amounts of virus. Syncytia formation is the main indicator of the cytopathic effect, or the effect on cells from the virus infection. Previous studies in the Reyes lab indicated that removing cholesterol from Vero/hSLAM cells during transfection with H and F viral plasmid reduced the cytopathic effect (unpublished results). The purpose of this experiment is to determine if treating Vero/hSLAM cells at different stages of the measles infection cycle will effect virus formation and the cytopathic effect. This experiment involved treating Vero/hSLAM cells with MBCD at various stages of the measles infection cycle. MBCD is a sugar compound that sequesters cholesterol from cells and disrupts lipid rafts. One sample group was treated before virus infection, another sample group was treated after virus infection, and the final sample treated the virus itself with MBCD. The measles virus used contains a red fluorescent protein, which allowed for the imaging of syncytia formation. Virus particle formation was quantified through viral kinetic measurements in Vero/hSLAM cell samples. The experiment is still in the first stage, which is treating the Vero/hSLAM cells with MBCD before virus infection. Initial results indicate a small increase in virus formation when samples are treated with 2.5 um MBCD solution pre-infection. Higher MBCD concentrations have reduced viral titers.
Undergrad team 1: Evolution of dispersal and population stability in small metapopulations
K. Harrison Holmes, Perry Olliver and Chalet Taylor
Abstract. Dispersal is a key life history trait in many vertebrates, especially those living in metapopulations—arrays of discrete habitat patches connected demographically by dispersal. Among the best known metapopulations is the American pika (Ochotona princeps), inhabiting ore dumps in the ghost mining town of Bodie, California. Members of this lab have studied the evolution of dispersal in this metapopulation in the field and with models for decades. Nevertheless, key model elements have proven nearly impossible to estimate precisely. Therefore, we have developed artificial metapopulations of confused flour beetles (Tribolium confusum) to examine dispersal under controlled conditions. Here we show that dispersal may be a tool to protect against population collapse, in the midst of environmental catastrophe. Stochastic and deterministic mathematical models were developed using data from our artificial metapopulations, comprising 5 patches—a central “hub” connected to 4 identical patches by tubes through which beetles could disperse. In accordance with other models of dispersal, adaptive dynamics analysis of our model suggests that a dispersal rate of zero is both evolutionarily uninvadable and attracting in metapopulations with no density-independent extinction of patches. However, when metapopulations suffer such catastrophic extinctions, dispersal can evolve and decrease the likelihood of metapopulation extinction.
Undergrad team 2: Analysis of spatially correlated extinction and its relevance to population dynamics of North American pika (Ochotona princeps) at Bodie, California
Sabrina Jones and Andrew Nemecek
Abstract. American pikas are small, egg-shaped mammals that live obligately on talus in the mountain regions of western North America. At the turn of the 20th Century, pikas colonized ore dumps at the ghost mining town of Bodie, California, on the eastern slope of the Sierra Nevada due east of Yosemite National Park. In the 1970s, Andrew Smith proposed that Bodie represents a true metapopulation, with ore dumps playing the role of island patches. This interpretation was challenged in 2002 by Michael Clinchy and colleagues, who argue that the data from the site can be interpreted as exhibiting conventional mainland-island dynamics, with islands suffering correlated extinctions. Since then, a much more detailed data set of pika population dynamics at Bodie has been compiled. We tested Clinchy et al.'s correlated extinction model against this new data set. Here we present preliminary results of this analysis.
BIO 298 team 1: Effects of female breast cancer awareness on male breast and prostate cancers
Lorida Llaci, Jaron Johnson and Todd Pelech
Abstract. In 1985, breast cancer awareness month was implemented in the United States. Since then, breast cancer has received an enormous amount of attention from researchers, funding agencies and the public. Our goal was to determine the impact of this focus on trends in incidence and mortality for both female and male breast cancer, and to compare these trends to those for prostate cancer over the same time period using data from the Surveillance Epidemiology and End Results (SEER) database from the National Cancer Institute. Here we show that awareness has an effect on mortality rate. We also discovered that both male and female breast cancer have a similar negative trend in case fatality rate. Prostate cancer mortality has also declined over time but at a significantly different rate than breast cancer. This study suggests that the large amount of attention that female breast cancer receives is not hindering progress for male breast and prostate cancers.
BIO 298 team 2: The effect of climate change on a potential HIV-malaria syndemic in South Africa
Elyse Conley, Nicholas Roberts, Ryan Maziarz, Matthew Glynn and Dakota Martinez
Abstract. Human immunodeficiency virus (HIV) and malaria are among the most pressing global health concerns, together causing more than 4 million deaths annually. Pathological interactions between HIV and malaria increase the severity of illness and fuel the spread of both diseases. South Africa grapples with a large HIV-infected population but does not currently have a climate suitable for malaria transmission. However, this could be reversed by global climate change in coming decades. Here we show that incidence of both HIV and malaria are expected to increase when the two occur syndemically. In particular, our mathematical model of these diseases in South Africa predicts that, during a syndemic, mean number of cases of HIV will increase from 15.6 to 16.2 HIV positive cases per 100,000 people while malaria cases increase from 35.2 to 39.5 per 100,000 in 10 years. Extrapolated across all of South Africa, these results suggest HIV and malaria burden will increase by almost 300,000 and two million cases, respectively. We hypothesize that substantial fluctuations in temperature and precipitation, leading to unstable seasonal malaria epidemics, could cause the actual impact of the introduction of malaria to be much greater than suggested by this analysis.