REU students will work to creatively shape the projects to match their interests. REU students will be full participants in all usual lab activities including lab meetings and journal clubs. Mentoring and support will be provided throughout the REU experience as described in the subsequent sections, and will enable students to grow as independent scientists.
Professor Kim Lewis and Research Scientist Anthony D’ Onfrio
Research Project Summary: The goal of the project is to discover and characterize new antimicrobial compounds. The project brings together two experts in antimicrobial discovery, Kim Lewis and Anthony D’Onofrio. REU students will screen a library of synthetic compounds, but in addition, attractive antimicrobial-producing microorganisms will be specifically captured from environments where their presence will be determined by their DNA signature, obviating traditional Petri dish isolation. The screen will uncover compounds acting selectively against a given pathogen, providing a new type of specific antibiotics. The compounds will be characterized for activity against a variety of human pathogens.
Student Involvement in Project: Under the direction of Drs. Lewis and D’Onofrio, the REU students will screen a compound library for selective activity against Borrelia burgdorferi, the causative agent of Lyme disease, and screen producing microorganisms against E. coli and S. aureus. Once compounds are identified, their mechanism of action will be studied.
What Students will Learn: Through this interdisciplinary work, the students will gain first-hand experience in experimental design, and in current techniques in microbiology and natural product chemistry.
Broader impacts of this project: There is a great unmet need for new antimicrobials, and this project will examine novel approaches to their discovery – species-selective screening; and focused access to attractive producers. Identifying compounds will validate these approaches, leading to their broad application. Beyond this study, the project will provide students with fundamental skills needed to address a broad range of questions in microbiology, natural product chemistry, and drug discovery.
Calcium and Redox Signaling in the Reproductive System
Associate Professor Erin Cram and Assistant Professor Javier Apfeld
Research Project Summary: The reproductive system of the nematode worm C. elegans is a highly-optimized assembly line for producing offspring. Oocytes develop in the oviduct and are ovulated into a tissue called the spermatheca, where they are fertilized. The spermatheca then contracts to push the fertilized eggs into the uterus. The process repeats every 20 minutes or so until >300 babies have been produced. The goal of this project is to understand how mitochondria in the reproductive system contribute to the amazingly robust success of C. elegans reproduction, and how mitochondria shapes, sizes, or roles might change as the animals age. We expect to identify genes and processes that are important, not just for worms, but in reproductive biology in all animals.
Student Involvement in Project: Students will help design experiments to reveal the importance of mitochondria in the reproductive system. Dr. Apfeld will focus on germline (oocyte) aging and Dr. Cram on the role in the somatic gonad (the smooth muscle-like cells that keep things moving through the system). We know mitochondria are needed for energy, but they also play very important roles in calcium and redox signaling, which are critical for cell function. Students will select candidate genes to study and will design and test their own hypotheses about how these genes might affect mitochondrial and reproductive system function.
What Students will Learn: Students will learn the fundamentals of designing, implementing, and interpreting experiments and communicating their results to others. They will learn how to disrupt gene function in C. elegans using RNA interference and genetic approaches including CRISPR-Cas9, will perform molecular cloning techniques including PCR, DNA electrophoresis, and DNA purification, will help make their own transgenic nematodes, and will visualize fluorescent proteins in living cells using 4D confocal microscopy. Students will learn how to explain what they are doing to a broad range of scientists and non-scientists.
Broader impacts of this project: Our students will learn to use the tools of molecular cell biology and genetics to address scientific questions. Through working in our research team, they will gain in confidence in themselves as capable scientists. Our program is designed to also help them build leadership skills and to learn how to communicate their passion for science to others. This will help them serve as ambassadors for STEM education when they return to their home institutions and move forward in their careers.
Mechanisms of UV-induced skin repair in a regenerative vertebrate
Assistant Professors Justin Crane and James Monaghan
Research Project Summary: The exposure of skin to UV radiation causes damage to cellular structures, alters the composition of the extracellular matrix and generates DNA breaks, accelerating the natural aging process. Lower vertebrates such as the axolotl Salamander have the ability to regenerate limbs and can repair skin wounds scar-free, serving as an optimal model organism to study skin repair in the context of UV-damage. REU students will investigate the biology of the UV-damage response and repair process in Axolotl skin in comparison to traditional laboratory mice. This project will bring together an expert in skin aging, Justin Crane, and an expert in regeneration, James Monaghan, to determine how a regenerative vertebrate uniquely handles the program of cell cycle arrest, apoptosis and DNA damage resulting from UV exposure.
Student Involvement in Project: Under the direction of the professors, the students will test cell proliferation and damage at various time points following UV exposure in both salamanders and mice. Students will assess how the structures of various layers of skin (epidermis, dermis, hypodermis) are affected by UV radiation in each model organism and which cells are most susceptible to cell death or proliferative arrest. Finally, students will discern the rate at which each organism repairs the affected tissue over time following UV exposure.
What Students will Learn: Through this work, students will gain considerable experience in generating testable hypotheses, designing experiments, and in performing immunohistochemistry and microscopy. We expect the data generated by the students will provide a basis for a scientific publication that expands our knowledge of the optimal repair processes necessary to fully restore skin after UV-exposure.
Broader impacts of this project: Discoveries that improve skin repair and regeneration have vast implications for a host of conditions, including burn injuries or wounds, chronic infections and skin cancer. Having students compare Axolotl and mouse mechanisms of cellular repair will provide students with a strong foundation to study cell and molecular biology.
Mitochondrial lineage in developing oocytes
Professor Konstantin Khrapko and Assistant Professor Dori Woods
Research Project Summary: The mitochondrial DNA mutator mouse is a unique animal model where different mitochondrial lineages within individual cells are naturally labeled with specific combinations of mutations. These specific mutation combinations allow us to trace mitochondrial lineages within a cell in the same way that the ancestry of individuals within human populations can be determined based on mtDNA mutations. This project unites an expert in ovarian development (Dori Woods) with an expert in mitochondrial genomics and aging (Konstantin Khrapko) to identify the ancestry of individual mitochondria/mtDNA molecules in oocytes. Since mitochondria are maternally inherited, this study is highly pertinent to the mechanisms of mtDNA inheritance and to how we protect ourselves from mtDNA mutational meltdown. This work will be a synthesis of two complementary approaches: reproductive aging with emphasis on mitochondrial function, and intracellular mitochondrial genomics.
Student Involvement in Project: The students will be exposed to several state-of the-art techniques, including individual sorting of mitochondria, full-genome single-molecule PCR, and highly multiplexed next generation sequencing. Most importantly, the students will be confronted with unique and novel data that will need interpretation. The students will participate generating novel hypotheses and the planning of new experiments aimed at testing these hypotheses. Interpreting ancestry/populational dynamics data is particularly suitable for students because it is both intuitive and engaging.
What Students will Learn: The students will acquire basic laboratory techniques, such as PCR and agarose gel electrophoresis, record keeping, and good laboratory notebook practice. Additionally, they will become acquainted with the basics of modern high-tech genomics approaches such like next generation sequencing. Students will have daily interactions with supervisors, graduate students, and postdocs, and will participate in general lab meetings and be required to describe their work in a 15-minute oral presentation at conclusion of their training. Usually successful students get to co-author a paper involving their work.
Broader impacts of this project: Our students will learn important skills during the REU period that will facilitate their scientific discoveries and prove valuable outside of the classroom and laboratory environments. The ability perform hypothesis driven research and analyze data sets hones organizational, analytical, and problem solving skills that promote stronger academics and reflect well in the workforce, even outside of science. Additionally, students will strengthen their abilities to effectively communicate complex ideas, as promoted through participation in lab meetings as well as the oral presentation, and, when warranted, in writing if co-authoring a manuscript.
Transgenerational effects of immune challenge in an insect model organism
Associate Professors Wendy Smith and Rebeca Rosengaus
Research Project Summary: We are using the tobacco hornworm Manduca sexta to identify genes responsible for metabolic, immunological and developmental changes elicited in offspring following exposure to bacteria and fungi in the parental generation. The recognition that the environment impacts both gene expression and inheritance has represented a major paradigm shift in our understanding of the interdependence between physiological responses and evolutionary change. The proposed research includes an integrated approach to the study of the dynamics between parental responses to microbial exposure and the overall future wellbeing of their progeny.
Student Involvement in Project: Students will help to develop and test hypotheses regarding the effects of exposure to pathogens on mothers and offspring. Under the direction of Rebeca Rosengaus, the REU students will focus on the effects of bacterial and fungal exposure on offspring development and immune responsiveness. Under the direction of Wendy Smith, students will focus on transcriptomic changes in mothers and offspring that result from maternal infection.
Students will Learn: Students will gain experience in generating hypotheses, experimental design, and techniques to explore mechanisms that control animal development and immunity including enzyme assays, imaging, and preparation and analyses of samples for next generation RNA sequencing.
Broader impacts of this project: The combined physiological and genomic approach will reveal novel mechanisms underlying transgenerational effects of environmental stress. Given that the regulation and expression of genes related to immunity and development are highly conserved, the results of this research program will be relevant to the study of transgenerational effects in other phyla.