The Hood lab is currently funded by 2 NSF and 1 NIH award.
NSF EPSCoR AWARD, 2017-2021
Genome to fitness: An analysis of the stress response in Peromyscus
Awarded to Kiaris and Hood
This is a collaborative proposal between two EPSCoR jurisdictions aiming to dissect the genomic basis of stress response. By using Peromyscus maniculatus as a model and by applying a combination of genomic analyses coupled with stress tests at the cellular and organismal level, investigators from the University of South Carolina (SC), Claflin University (SC) and Auburn University (AL) will explore how genomic differences in individual animals determine the fitness of the organisms by focusing on the regulation of the unfolded protein response (UPR). The specific objectives of the project are: 1. To identify and validate Quantitative Trait Loci (QTLs) correlated with UPR response in P. maniculatus. 2. To establish cultures of primary fibroblasts from P. maniculatus and to perform analysis of the UPR in culture. 3. To monitor the response of P. maniculatus in different environmentally-relevant diets. 4. To associate genomic signatures and variation in the UPR profile of fibroblasts to variation in animal survival and reproductive performance under semi-natural conditions (WILL BE COMPLETED AT AUBURN). Each participating Institution brings specific expertise in the project that range from genomics to evolutionary biology and from biostatistics to endoplasmic reticulum stress analyses. Several comprehensive steps for the long-term sustainability of the proposed project, far beyond the award period, will be implemented. Those involve a detailed plan for securing outside grant support, income generating actions through offering of specialized services provided to outside investigators.
Any condition that deregulates homeostasis is capable of inducing stress and in turn, to impact the
relative condition, reproductive performance, and survival of individuals. In order to cope with stress organisms have evolved an array of specific biochemical and physiological responses, a subset of which is the unfolded protein response that follows stress of the endoplasmic reticulum (ER). As is true of many components of the integrative stress response, it is expected that variation in an individual’s capacity to undergo ER stress and subsequently, UPR will affect its relative ability to cope with challenging environments or stress-inducing stimuli. The overarching goal of this study is to identify the genes and epigenes responsible for variation in endoplasmic reticulum (ER) stress and the resulting unfolded protein response (UPR) and to characterize the physiological and fitness ramification of these differences in the North American deer mouse (Peromyscus maniculatus). The findings of the proposed study are expected to have a profound impact in the field of stress adaptation and fitness setting a paradigm for studies linking genomic signatures with the UPR and organismal fitness and is expected to set the basis for additional studies in the future in additional animal models and environmental stressors.
Besides its mere scientific value as such, the project will have a broad impact at various areas:
Through the specific research tasks of the proposal, a series of reagents, tools, and methodologies will be developed and optimized that will be made readily available to other investigators to assist them with their specific research needs.
Recruitment of new faculty with interest in stress biology, evolution and genomics at USC.
Establishment of a strong mentorship program applicable for all investigators ranging from undergraduate students to junior faculty
Exploitation of the capacities of the Peromyscus Genetic Stock Center (USC) and development of a new Rodent Performance Testing Lab (RPTL) at Auburn
Enhancement of several existing and development of new innovative courses for graduate students
Undergraduate student training in the lab
Special emphasis to train students from ethnic and other underrepresented minorities.
Implementation of an innovative grant mentoring system for postdocs that will prepare them to become
NSF CAREER, 2015-2020
Effects of mitohormesis on reproduction and longevity
Awarded to Hood
The hypothesis that there is a tradeoff between reproductive investment and longevity is a central tenet of biology. Because reproduction is energetically demanding, it has been assumed that reproduction stimulates the production of damaging reactive oxygen species (ROS), hastening senescence. Yet, several studies have now shown that oxidative damage is typically unchanged or reduced in reproductive individuals when compared to non-reproductive controls. In addition, the new theory of mitohormesis suggests that low ROS generation, as occurs during reproduction, not only lowers oxidative damage but it may also protect cells from future oxidative damage that contributes to aging. Most published studies that have evaluated the interaction between reproduction and oxidative damage have limited observations to young breeders, so the possibly that oxidative damage contributes to senescence later in life cannot be ruled out. The goals of this CAREER proposal are to 1) test whether reproduction protects against future oxidative damage and to 2) determine if mitochondrial function and the cellular response to an induced oxidative stressor change with age in a continuously breeding species, the house mouse (Mus musculus). Finally, given the potentially protective effects that reproduction has on processes that induce aging, a third goal of this project is to 3) evaluate the interaction between reproduction and longevity in female mice by comparing age at death in females that have bred few times versus those that have bred many times. Several cutting-edge techniques will be employed in this investigation including measurements of ROS production from mitochondria and oxidative damage in organs that commonly decline during senescence. In addition, respiratory control ratio, electron chain complex activity, mitochondrial biogenesis, abundance of uncoupling proteins and levels of endogenous antioxidants will be evaluated. The impact of treatment on insulin-like growth factor-1 and telomere length will also be evaluated as indicators of the impact of treatment on aging.
The proposed set of experiments will challenge a central tenet of biology that reproduction comes at a cost to longevity. This investigation will provide a detailed assessment of the role that reproduction plays in the accumulation of ROS and in resistance to stressors that hasten aging. Unlike many studies that have searched for a mechanistic basis for the tradeoff between reproduction and longevity, this study will ask whether such a tradeoff really exists. Whether this study supports or refutes the idea that ROS produced during reproduction contributes to age, the project will transform the study of life-history evolution, and the outcome will be a better understanding of the mechanistic relationship between aging and reproduction.
Research on the interaction between mitochondrial function, reproduction, and longevity will be used as a platform for education and the improvement of science literacy in the state of Alabama. In collaboration of with local biology teachers, integrative and inspiring lesson plans with labs will be developed for 7th and 9th graders (the grades at which mitochondria are included in the Alabama State Course of Study for Science Standards). These lessons will feature the proposed research on mitochondria and aging. By training teachers throughout Eastern Alabama on application of the lessons and by submitting the lessons to the Alabama State Department of Education, these lessons could be used in every 7th and 9th grade biology classroom in Alabama. In addition, Auburn graduate students will be challenged to commit to regular participation in outreach in a graduate-level seminar on Mitochondria and energetics. These students will modify the aforementioned lessons for Auburn Universitys Getting Under the Surface program that invites 5th grade students and their parents to campus to participate in an interactive laboratory run by faculty and their students. This will be a great opportunity for these students to hone the important skill of taking a complex biological concept and making it understandable and relevant to people in their community.
The mechanistic basis for improved metabolic health in females following lactation
Awarded to Hood and Kavazis
Breastfeeding not only improves the health and development of the suckling young but it also confers lasting benefits to the health of mother including reduced incidence of obesity and type II diabetes. Following weaning, females that lactate display fewer visceral adipocytes, lower fasting glucose, increased insulin sensitivity and reduced circulating lipids relative to females that give birth but not suckle their young and females that do not reproduce at all. By the lactation reset hypothesis, it has been proposed that lactation plays a central role in resetting a female’s risk of metabolic disease yet the mechanisms responsible for this effect remain largely unexplored. The goal of the proposed project is to evaluate the mechanisms responsible for differences in whole animal and cellular metabolism between female rats that have suckled their young to weaning (PL), age-matched female rats that have given birth but not suckled their young (P), and aged-matched female rats that have not reproduced (NR). Rats will be used as our model organism for this study. Whole-animal metabolic rate and mitochondrial profiles of liver, skeletal muscle, and white adipose tissue will be compared between all treatment groups after the PL rats are weaned and again 3 months later. These values will be evaluated relative to pre-breeding, late pregnancy, and peak lactation values to determine if patterns of metabolism are indicative of the re-establishment to pre-breeding values by lactation. Based on their roles in adjusting lipid oxidation and mitochondrial biogenesis, the relative expression of peroxisome proliferator activated receptors and PCG1-alpha transcriptional coactivator will be evaluated in each group for their potential to stimulate long term physiological changes in metabolism following lactation. In addition, variation in oxidative damage will also be compared between groups as indicators of mitochondrial ability to maintain organ health. The results of this work will improve our understanding of how whole animal metabolism and cellular physiology are improved by lactation and provide targets for future studies evaluating interventions for women that are unable to nurse their young for an extended period and women who don’t reproduce.