Mentors and Projects Available to Choose From Summer 2021
Debbie Crans and the Crans Laboratory
Project Description: We work on biological and biomedical chemistry and have project exploring projects relating to cancer and in tuberculosis. We develop and characterize compounds with improved anticancer properties against cancers that are otherwise resistant. Last year the discovery of the novel approach received the nobel prize.
We develop compounds that enhance virus replication and that combat cancer and are targeted to be used for immunotherapy.
The student will either be involved in compound synthesis or explore its more of action through mechanistic studies. One mechanism that we have been exploring is signal transduction mechanisms.
Mentoring Plan: Mentoring in my group is a joint endeavor. The assigned graduate student mentors, Heide Murakami and Cameron Van Cleave both 4th year graduate students and experienced mentors, I and the entire group participates and meets with the student.
Department of Biochemistry and Molecular Biology
Project description: For projects in our lab, we use a combination of cell biological and biochemical approaches to (1) study the mechanisms that ensure mitotic chromosome segregation fidelity, and (2) investigate the links between chromosome mis-segregation and cancer initiation.
An ideal cancer therapy would specifically target cancer cells for destruction while leaving healthy cells in the body unharmed. An exciting area of research in cancer biology is the identification of differences between cancer cells and healthy cells so that drugs can be developed that only kill the cancer cells. The idea is that cancer cells, along their path to becoming cancerous, change in a manner that leads to the development of defects in certain cellular processes. This results in vulnerabilities in cancer cells such that they become dependent on certain cellular factors for survival. In a hypothetical example, “protein X” is depleted from both cancer and non-cancer cells. This causes the cancer cells to die since they require protein X to survive. Healthy cells, on the other hand, do not harbor the defects and vulnerabilities of the cancer cells, therefore they are not affected by the depletion of protein X. In such a scenario, a drug that inhibits the function of protein X is an ideal candidate for an anti-cancer therapy. Since only the cancer cells require protein X to live, the drug kills cancer cells, but healthy cells remain alive and well. In our lab, we have discovered that many cancer cells exhibit certain defects during the process of mitosis, or cell division. Specifically, cancer cells have problems connecting chromosomes to the cellular fibers (microtubules) that drive the chromosomes to the metaphase plate. In collaboration with Dr. Patrick Paddison (Fred Hutchinson Cancer Research Center, Seattle, WA), we recently demonstrated that tumor cells derived from patients with glioblastoma (GBM) harbor these defects, resulting in the cancer cells’ absolute dependence on two mitotic proteins, BubR1 and BuGZ. Strikingly, depletion of these proteins kills GBM cells, but not healthy, non-cancer cells. In this proposal, we will test if inhibition of these mitotic proteins using small peptides will result in defects that leads to cell death in cancer cells but not healthy cells. The studies here will provide a platform on which to build new cancer therapeutic strategies for GBM and other incurable cancers.
Two specific REU projects are (1) Determining how forces are generated between mitotic chromosomes and mitotic spindle microtubules; or (2) Testing if small fragments of mitotic proteins can act as inhibitors of mitotic progression to result in cell death of cancer cells, but not healthy cells.
Mentoring plan: Students will work with Amy Hodges, Jeanne Mick and Keith DeLuca. I am committed to providing training and mentorship to an REU student. I have trained, with the help of my research team, 28 undergraduate students and am currently mentoring two. Upon acceptance into the lab, I will work together with the REU student to develop a research project based on the student’s area of interest and available projects in the lab. In addition, I will work with the student to create an individual development plan, which will include the following: Experimental training. The student will be trained in cell biological techniques, high- and super-resolution imaging, and biochemical assays and approaches. Technical training will be provided by a graduate student mentor, a senior research scientist, and myself (Dr. DeLuca). In addition, our lab is highly collaborative with other labs both inside and outside of Colorado State University, and these collaborations offer abundant opportunities to learn new research skills. The student will meet with his or her graduate student mentor daily to discuss experimental design, results, and future experiments. In addition, the student will meet once a week with Dr. DeLuca to discuss progress on experiments. Engagement into the laboratory. The student will be provided both bench space to carry out experiments as well as desk space in the lab to work on experimental design, to carry out data analysis, and to serve as a “home base” when on campus. The student will attend weekly lab meetings and present their data at lab meeting once a semester. In addition, the student will be encouraged to attend internal weekly Departmental seminars and weekly seminars delivered by outside speakers. Development of oral scientific communication skills. The student will be provided with opportunities to present both informal and formal presentations in our department and at Colorado State University (including campus-wide poster presentations). In addition, the student will attend the regional Front Range Cytoskeleton meeting during the summer (and will present a poster if projects have progressed). Development of written scientific communication skills. This training will involve iterative development of abstracts (and possibly manuscripts) with intensive support from Dr. DeLuca. Training in ethics and responsible conduct in science. Scientific ethics will be discussed with the student on a day-to-day basis in terms of reporting scientific findings, generating figures, and communicating science. Participation in job-seeking workshops and accessibility to career development resources. These opportunities will be provided by CSU, the College of Natural Sciences, and the Biochemistry Department. Dr. DeLuca has been actively engaged in seeking out and providing experiences to both undergraduate and graduate students that allow them to explore and prepare for future careers.
Laboratory for Air Quality Research, Department of Mechanical Engineering
Project description: Bioaerosols that include viruses, bacteria, pollen, and spores are small particles of biological origin. Bioaerosols have wide ranging effects from being linked to transmission of infectious diseases (e.g., SARS-CoV-2) to the formation and properties of ice clouds. Our group, along with scientists at Handix Scientific (an atmospheric instrument company in Colorado), have recently developed the fluorescent portable optical particle spectrometer (F-POPS). F-POPS is a lower-cost optical particle counter that can measure size, number, and fluorescence of bioaerosols. When deployed in a network, these will allow for scalable measurements of the emissions and concentrations of bioaerosols, precursors to understanding their impacts on air quality, human health, and climate. The project goal is to characterize the instrument to measure size, number, and fluorescent behavior of natural and man-made, indoor and outdoor, biological particles.
Natural (e.g., plants) and man-made (e.g., humans) sources emit small biological particles into the indoor and outdoor air, e.g., pollen in the case of plants and virsuses/bacteria in the case humans. We have developed a low-cost light-based instrument that can measure the properties of the biological particles that can be used to study their emissions and impacts on indoor and outdoor air.
The REU student will first work on a literature review to identify suitable (e.g., non-toxic, inexpensive) bioaerosol proxies to be studied in a laboratory setting. They will then program a high time-resolution, data acquisition system to perform real-time analysis of scattered and fluoresced data for single particles measured using the F-POPS. Finally, they will characterize our custom F-POPS instrument for several different bioaerosols at different concentrations and environmental conditions (e.g., temperature, relative humidity) and deploy the F-POPS in a pilot study to sample ambient bioaerosols. At the conclusion of the REU period, the student will learn how optical particle counters can be used to measure properties of bioaerosols.
Mentoring plan: Shantanu Jathar and Gavin McMeeking and his staff at Handix Scientific will provide mentoring depending on the stage of the project.
Extracellular Regulation of Metabolism Laboratory, Health and Exercise Science Department
Project description: Our laboratory studies how skeletal muscle, the largest tissue in the human body, communicates with other cells and organs in the body.
Skeletal muscle, which allows us to perform physical activity, releases factors throughout the body that allow for communication. We study how skeletal muscle communicates in health and disease.
In our laboratory, an REU participant will perform tissue culture experiments on skeletal muscle cells and analyze the release and composition of extracellular vesicles, an emerging mode of intercellular communication.
Mentoring plan: Day-to-day mentoring will be mainly by Zack Valenti, a Ph.D. student in the lab. Zack is currently mentoring an undergraduate student in the laboratory and has a passion for mentoring trainees. I have been mentoring Zack on how to be an effective mentor and will continue to do so. The REU student will have opportunities to speak with me at least twice a week. Once in our weekly lab meeting and an additional weekly small group meeting between myself, Zack and the REU student. As I have done in the past with undergraduate trainees, I will also ensure that I spend time with the REU student 1-on-1 to discuss general approaches for success both within and outside of academia.
Microbiology, Immunology and Pathology Department
Project description: The lab focuses on diagnostics and therapeutics for neurotoxic diseases including prions, tuberculosis meningitis, pollution induced Alzheimer’s disease, companion animal cognitive dysfunction and viral neurotoxicity.
Understanding what happens in the brain when it is exposed to harmful things is critical for diseases like Alzheimer’s disease and other dementias. We focus on this so that better diagnostics and ways to treat people can be figured out and tested.
The REU student would assist a graduate student in analysis of a toxin induced inflammation within the brain. This work will help with the development of an ante-mortem diagnostic, which is critical for proper therapeutic intervention.
Mentoring plan: I will help with the training of the student, meet with the student weekly and include them in lab meeting and journal clubs. The participant will also work with Arielle Hay and Amanda Latham.
Project description: We study the signaling ways that control steroid hormone production in the molting gland that allows the crab to respond to a variety of external and internal cues that determine when the crab molts or sheds its shell.
Crabs, lobsters, and shrimp are ecologically and economically important crustaceans in marine environments. The hard, calcified exoskeleton provides protection and support, but restricts growth. As a result, these animals must periodically shed the exoskeleton, a process called molting. Upon molting, animals stretch the new exoskeleton before it hardens, providing more space for tissue growth. The entire process is controlled by molting hormone produced by a pair of molting glands. The activity of the molting gland is controlled by environmental signals mediated by the nervous system. Much remains to be known about the signaling genes that control the molting gland, in particular the genes required for (1) committing the animal to molt and (2) repressing the molting gland after the animal molts. Commitment is a “point of no return” decision that is critical for survival and growth in all crustaceans. Repression prevents molt induction until synthesis and calcification of the exoskeleton is completed. This collaborative project involves a team of investigators from four universities who will use state-of-art DNA and peptide sequencing technologies to identify genes and proteins essential for the activation, commitment, and repression of the molting gland and its regulation by environmental signals. The data generated will be made available to researchers so that they can better understand how to manage fisheries, develop effective aquaculture practices, and mitigate the effects of pollutants and climate change. Three postdoctoral fellows, four graduate students, and 6-8 undergraduates will receive training in advanced molecular techniques and bioinformatics. Learning activities on the effects of temperature and acidification on molting in cherry shrimp will be developed to engage ethnically diverse and rural students in the life sciences. Training workshops will be offered to six teachers recruited from junior high and high schools in northeastern Colorado, and impacts on student and teacher learning will be assessed
An REU participant will conduct bioinformatics and experimental analysis of signaling pathway genes.
Mentoring plan: The day-to-day mentoring will be the primary responsibility of the postdoc scholar hired to work on the project. The REU student will meet every week with Dr. Peebles (when I’m in town) to discuss career goals, and other research related topics. The REU student will go through safety training at the start of the program. The REU student will receive in-lab safety training as well as an online safety course developed by CSU EHS. The REU student will be trained by his/her graduate student mentor in experimental techniques. The mentor will work closely with the REU student to plan and set-up experiments and interpret data. The REU student will also receive guidance on how to search for research articles in online databases, read technical research articles, and report scientific findings in a poster format. Success of the REU experience will be evaluated through student and mentor feedback, through progress toward research goals, and through an end of summer presentation.
Erin Osborne Nishimura
Department of Biochemistry and Molecular Biology
Project description: Embryos start out life as a single cell but quickly diversify into the bones, muscles, neurons, and skin that make up a plant or animal. Our lab is interested in how these diverse cell types arise. Generally, we address these and other developmental biology questions using cutting-edge technologies like single-cell-resolution genomics and single-molecule imaging. Our research combines hypothesis-driven molecular experimentation and computational analysis.
Embryos start out life as a single cell, but their cells quickly multiply and diversity into the many cell types of our body. Our lab is interested in understanding how groups of genes are activated during these processes to carry out this cellular diversification. Though our work is relevant to all embryonic development, clearly human embryos are not ideal to work on. For this reason, we use the small nematode worm called C. elegans as a model system. C. elegans are 1 mm long, non-pathogenic soil dwellers with beautiful embryology. We can observe their development under the microscope over the course of a day. We work in conjunction with a large C. elegans community that has generated many tools and resources for the field, making discoveries speedy and fun.
We have a number of possible projects. Both in person and remote computational projects are available. We are currently engaged in two basic research fields. In the first, we investigate how localization of mRNA transcripts in early embryos is regulated and how it impacts embryonic development in the model system of the C. elegans nematode worm. These projects involve genetics, molecular biology, microscopy, deep sequencing, and computation approaches. In the second research area, we study how organs develop by using the intestine of C. elegans as a model system. We use genomics, genetics, microscopy, and molecular biology approaches to address how gene expression is orchestrated in developing intestines to form their characteristics as well as how the adult intestine responds to changing diets, infection, and the aging process.
Mentoring plan: REU participants meet with the PI for at least three structured one-on-one meetings during the summer. Interns will be assigned an in-lab mentor who will meet with the intern for weekly overviews of the project and will work one-on-one in the lab for trainings and explanations. The interns will present their work to the larger lab group in one round table discussion and one seminar-style presentation throughout the summer. Interns will be full members of the lab and will participate in lab meetings, journal clubs, symposia, and other events. We host a series of workshops during the summer on scientific writing and statistics and these are optional. We also organize events outside of the lab such as summer hikes, picnics and travel to nearby universities. These are also optional. An REU participant will also work with Meghan Costello and Jessica Hill.
Chemical and Biological Engineering Department
Project description: Simulations of Complex Dynamics in Biology. My lab is looking for REU students interested in computational research to work on one of 2 projects described below. Both projects are computational and will be mentored remotely; however face-to-face mentoring may be possible for part of the summer if circumstances permit. 1. Shape, forces and form: simulating the actin cytoskeleton. The actin cytoskeleton is the most dynamic part of the cellular cytoskeleton, responsible for many dynamic processes in the cell such as cytokenesis and cell migration. It is also the primiary determinant of cell shape. However, it is increasingly clear that the cytoskeleton is also involved in cellular decision making and is the site of mechanotransductive signaling. However, the cytoskeleton is a highly interconnected system. In our view, it is impossible to understand it without computer simulations. Many groups have responded to this challenge by developing computational platforms for simulating the cytoskeleton. This challenging project is for the computational minded student who enjoys programming to build a simulation of a portion of the cytoskeleton in order to understand the process of cell spreading on a surface. 2. Simulating epigenetic memory in plants. Plants, as sessile organisms must have the capacity to withstand environmental stresses without moving to more salubrious surroundings. To do this, plants have evolved a complex system of gene regulation that depends on maintaining a memory of previous environmental stresses. While plants have developed an array of impressive defenses, maintaining them at all times is expensive and likely detrimental to plant growth. Plants deal with this challenge by encoding the memory of a recent stress using epigenetic marks, which then modulate the plant response to future environmental stresses. Plants thus carry out a fairly complex computation to determine their responses by integrating readout from environmental sensors that report on current conditions with the history of previous conditions encoded into the plant’s epigenetic state. This project involves building a computational model of stress-induced epigentic memory in plants, to help understand how plants ‘think’.
We have two different projects on offer under the title: “Simulations of Complex Dynamics in Biology”. (1) There is something fascinating about viewing the image of a live cell under a microscope, since it looks like a little blob that is alive. What makes it breathe and twitch is an elaborate system of molecular muscles that is called the actin cytoskeleton. To help understand the actin cytoskeleton better, we would like to make a computer model of it, with the ultimate aim of understanding how cells spread and move. (2) We know that elephants can remember, but so can plants! Plants will remember that bug that took a bite from them, or that hot day they suffered through in August. Like us their memory fades. Also like us, their memory of environmental stresses helps them deal with the next one. This project is for developing a computational model of plant memory, based on what we understand of the molecular details of the process.
An REU student will read papers and write code to simulate the systems as outlined.
Mentoring plan: The REU participant will be mentored by me through meetings held twice a week to begin with. In addition, some mentoring will be provided by graduate students.
Quantitative Systems Pharmacology and Toxicology Research Group, Chemical and Biological Engineering Department
Project description: Characterizing the disposition and effect of foreign chemicals on human health using biologically based modeling underpinned by data. This work has implications for a wide spectrum of applications from optimizing drug dosing regimens to assessing the safety of industrial chemicals.
Foreign chemicals can have both positive effects on health (as in the case of therapeutic drugs) and negative effects (as in the case of many industrial chemicals). The project will involve examining how certain of these chemicals affect human health and how we can use our understanding of biology and chemistry to develop descriptions (mathematical models) of the relevant processes to predict how the body manages exposure to these chemicals and how these chemicals affect the body.
Students will learn the basics of pharmacology and toxicology and contribute to building useful quantitative models that could ultimately replace testing on animals.
Mentoring plan: The PI will provide the mentoring.
Microbiology, Immunology and Pathology Department
Project description: We are exploring why some people and animals are more likely contract a prion disease than others. We think the answer pertains to different levels of proteins in the body that help to prevent infection and we are studying these specific proteins in cell culture to validate that hypothesis.
We have previously generated cell lines that are either sensitive or resistant to infection with prions. Using RNA sequencing, we have identified key molecular pathways and associated genes differentially regulated between the sensitive and resistant lines. Our REU student would be working to help validate these RNA sequencing results in the lab using techniques such as ddPCR and western blotting. Based on these results, further exploration of expression levels of these genes will be done using CRISPR knockdowns and/or over-expression vectors. If remote work needs to continue, the REU student can assist with further analysis of our RNA sequencing results and other bioinformatic approaches to addressing our research question.
The participant will identify key molecular factors that contribute to susceptibility to prion diseases.
Mentoring plan: The student will primarily be mentored by 4th year CMB graduate student – Julianna Sun. Day-to-day training in lab techniques will be done by her. Additional help in the lab will be provided by Dr. Jifeng Bian (research scientist) and Jenna Crowell (lab technician) as needed. Dr. Glenn Telling will provide mentoring to the REU student through weekly feedback and progress checks. Dr. Telling will also provide mentoring feedback to Julianna Sun on ways to improve her mentoring if needed. Everyone in the lab will be available to answer questions and help troubleshoot any issues.