Palmetto Research Academy 2013 Opportunities

Dr. Jeffrey Anker, Clemson University—Developing Optical Strain Gauges for Passive Remote Strain Sensing
Strain measurements are essential for detecting mechanical problems early. Simple, easily addressed mechanical issues such as loose screws, overinflated tires, and fatigued structures can contribute to device malfunctions and adversely affect mission safety. A variety of strain sensors are available including resistive and capacitive strain gauges, ultrasound, x-ray diffraction, optical moiré pattern analysis, and video tracking. However, electronic strain gauges are often impractical to apply to large areas for imaging, or in small regions such as within bolts. X-ray and ultrasound analysis are impractical for distant remote measurements, and optical techniques such as motion sensing and moiré analysis are affected by the distance and angle of the object with respect to the camera. The goal of this project is to develop a passive strain indicating “sticker” that can be rapidly read by eye or camera based on color. The optical strain gauge comprises a bottom plate patterned with a series of colored lines, and a transparent indicator plate placed above the bottom plate. The indicator plate is patterned with a series of equally spaced lines to mask part of the bottom plate. Displacement of the indicator plate with respect to the bottom plate unmasks a new type of line visible through the “window region” altering the visible spectrum (see Figure 1). Strain guage principle
The challenge is to precisely fabricate, align, and analyze the signal during strain cycling. Two students will work together on this project to design and fabricate the devices and then apply them to bending and tensile strain measurements on metallic and rubber specimens. The approach is widely applicable to measuring strain in everything from tires and screws to growing plants and actively controlled smart materials. We will fabricate strain sensors by inkjet printing and photolithography and study the strain sensitivity of the devices and test the effect of camera distance and angle, and lighting intensity on the sensitivity by camera and by eye. Overall, students will develop an elegant technique and learn instrumental design, image analysis, and sensor calibration.

Dr. Scott Argraves, Medical University of South Carolina—Bone Formation/Remodeling in Wildtype and Cubilin-Haploinsufficient Mice
Megalin and cubilin are co-receptors that mediate cellular endocytosis of complexes of vitamin D binding protein (DBP)-25D. These two receptors are expressed by absorptive epithelial cells present in select tissues, including small intestine and kidney. Mice deficient in renal megalin expression excrete 25D and develop plasma deficiency of 25D and 1,25(OH)2D/calcitriol and bone disease. Similarly, mutations in dogs and humans causing cubilin dysfunction produce urinary excretion of 25D. We are investigating the hypothesis that spaceflight causes changes in expression of cubilin and megalin that would subsequently affect vitamin D metabolism and thereby cause deleterious effects on bone homeostasis. Current results indicate that: 1) cubilin and megalin are subject to epigenetic regulation based on their altered expression in response to 5-aza-2'-deoxycytidine (5Aza) and Trichostatin A (TSA), which influence DNA methylation and histone deacetylation, respectively; 2) cubilin is downregulated in the gut of mice that have flown on the space shuttle (STS-108); and 3) genes linked to epigenetic regulatory events, namely DNA methylation and acetylation, were also affected during spaceflight. Thus, the data are consistent with the interpretation that cubilin and perhaps megalin undergo epigenetic regulation during spaceflight that alters their mRNA expression. We plan to test the idea that alterations in cubilin and megalin expression are linked to bone physiology and homeostasis. To address this we will evaluate the impact of 5Aza and TSA upregulation of cubilin and megalin on bone formation/remodeling in wildtype and cubilin-haploinsufficient mice using microcomputed tomography (micro-CT) imaging and bone biomarker analysis.

The student participating in this project is expected to help analyze bone from mice treated with 5Aza and TSA. Time permitting, bones from both wild-type (i.e., normal) mice and cubilin-deficient mice will be examined. The student will be trained to use various methods needed for assessing bone physiology, which will likely include PCR-based analysis of gene expression, immunological analysis of bone phenotypic markers, and analysis of micro-CT data to quantify bone size, density, and volume. In addition to their involvement in the research project, the student will participate in 1) a journal club to discuss physiological consequences of spaceflight/microgravity, and 2) social and educational activities sponsored by the MUSC summer undergraduate research program.

Dr. Jamie Barth, Medical University of South Carolina—Nutritional Deficiencies in Response to Microgravity
In addition to the well-established detrimental effects on bone and muscle, spaceflight causes problems or complications with astronaut nutrition. The spaceflight environment results in a decrease in energy intake and can also cause a reduction in blood micronutrient levels and compromised calcium homeostasis, factors that are likely to impact other physiological systems. To examine the causes of nutritional deficiencies in response to microgravity we are using high-throughput technology to analyze gene expression changes occurring in the small intestine of mice flown on the STS-108 space shuttle mission. Preliminary results indicate that pathways relating to calcium absorption/transport and vitamin D metabolism are compromised by spaceflight, which may contribute to the deficiencies in serum calcium and calcium homeostasis that have been observed in astronauts exposed to microgravity. Furthermore, genes relating to chromatin remodeling and DNA methylation are altered by spaceflight, suggesting the possibility that microgravity induces epigenetic changes that underlie some of the deleterious effects of spaceflight. This project will explore the transcriptomic evidence that epigenetic changes occur in the small intestine and will seek linkages between these putative alterations and the observed changes in calcium absorption/transport and vitamin D metabolism pathways.

The student participant will work with Dr. Barth to learn and perform the following analyses that address these questions: a) DNA microarray (transcriptomic) data analysis, b) quantitative PCR analysis for validating observed changes in gene expression, and c) bioinformatic analysis for extracting and collating gene pathway and function information. The participant will also collaborate with the student involved in Project 1 to determine whether the observed alterations in the intestine may contribute to changes in bone structure and physiology. In addition to their involvement in the research project, the student will participate in 1) a journal club to discuss physiological consequences of spaceflight/microgravity, and 2) social and educational activities sponsored by the MUSC summer undergraduate research program.

Dr. Sakamuri Reddy, Medical University of South Carolina—Osteoclast (OCL) Progenitor Growth/Differentiation and Bone Resorption Activity
Evidence is accumulating that unloading of the skeleton due to spaceflight or to an altered gravitational environment results in a reduction of bone mineral density. Astronauts experience 13-20% of loss in bone mass, which leads to fracture risk. In addition, bone loss is associated with many pathological conditions such as osteoporosis and bone metastasis mainly due to increased number of osteoclasts (OCL), the bone resorbing cells in bone microenvironment. It has been shown that microgravity (µXg) favors osteoclastogenesis, but the molecular basis of bone loss in astronauts during space flight is unclear. Using the NASA developed Rotary Cell Culture System (RCCS) we have demonstrated that simulated µXg causes increased OCL differentiation. Furthermore, OCL differentiation under µXg conditions stimulates expression of CXC chemokines such as CXCL2, 4, 7 & 14. Therefore, we hypothesize that µXg-based induction of CXC chemokines modulates osteoclast differentiation/bone resorption activity. To test this hypothesis, we are focusing on the potential of µXg-induced CXC chemokines (CXCL2, 4, 7 & 14) to stimulate osteoclast (OCL) progenitor growth/differentiation and bone resorption activity in mouse bone marrow cultures. Additional goals are to test whether CXC chemokines stimulate chemotaxis of preosteoclast cells in vitro and assess whether µXg-induced CXC chemokines modulate RANKL-RANK receptor signaling critical for OCL differentiation and bone resorption activity. These studies may identify potential novel therapeutic targets and allow development of rational approaches to control bone loss and fracture risk due to enhanced osteoclast activity in astronauts during space flight missions.

The student participating in this project will learn techniques and molecular methods necessary to test how cultured osteoblasts respond to chemokine and/or related stimuli. This will likely include: a) cell culture methods for growing, maintaining and differentiating osteoclasts; b) staining procedures for immunological and phenotypic characterization of treated cells; and c) RNA isolation and PCR amplification methods for investigating changes in expression of osteoclast (lineage) marker genes. In addition to their involvement in the research project, the student will participate in 1) a journal club to discuss physiological consequences of spaceflight/microgravity, and 2) social and educational activities sponsored by the MUSC summer undergraduate research program.

Dr. Frank Chen, University of South Carolina—Advanced Solid Oxide Cell Technology to Support NASA’s Planetary Exploration Missions
NASA’s mission to explore inhospitable environments such as the Moon and Mars requires the substantial use of electrical power and oxygen for extremely long durations to support manned missions. The unitized regenerative ‘closed loop’ solid oxide fuel cell (SOFC) cycle is one of the most attractive choices for supplying power for communications, advanced life support, survey equipment and rovers, and oxygen for crew habitats. This proposed Palmetto Academy Site will be based at the SOFC Center of Economic Excellence at the University of South Carolina (USC) and the project will construct and test a solid oxide fuel cell for unitized regenerative operations, i.e., to produce electricity under the fuel cell mode and to produce oxygen (and syn-gas (H2-CO) at the same time) by steam and carbon dioxide co-electrolysis. The SOFC program at USC has active interaction with the SOFC team at NASA Glenn Research Center in Cleveland, OH.

This project will support one Palmetto Academy fellow (undergraduate or graduate student) to work in the SOFC program at USC and provides a unique, intensive and rigorous educational and training curriculum in multidisciplinary science and engineering areas. The student will be involved with hand-on experience of every aspect of building an advanced solid oxide fuel cell, including novel engineering materials synthesis, solid oxide cell component fabrication using freeze-drying tape-casting, power generation through fuel cell mode, oxygen and syn-gas production through electrolysis mode. Further, the student will be introduced to the fundamental knowledge of nanostructured materials synthesis, catalyst development, fuel cell and electrolysis operations, material science and engineering, electrochemistry, as well as data analysis and interpretation. The student will be mentored by the PI and will be working together and guided by a group of post-doctoral fellows and graduate students in the PI’s laboratory. The student will be trained for problem solving skills, team working spirits, technical report writing, oral communication and presentation skills.

This Palmetto Academy project is aimed at making aware to the student the critical needs in electrical power and oxygen for manned trips to fulfill NASA’s planetary exploration missions. The unitized regenerative solid oxide fuel cell technology will be continuously conducted in the PI’s laboratory at USC beyond the completion of this Palmetto Academy project, with emphasis on new materials development to improve the device performance and durability. The PI will encourage and provide support to the student involved in the 2013 Palmetto Academy project to continue working on this topic upon completion of the summer program. The cutting edge technology designed in this project will help to stimulate the students’ interest in science and engineering, and ultimately inspire the student to pursue NASA-relevant research and development positions.