The mobility of autonomous walking robots is an essential characteristic in their operation. Due to currently imposed constraints in battery technology, the optimization of robotic locomotion for energy efficiency is paramount. Previously, elastic payload suspension has been employed to reduce the cost of transportation in a hexapedal robot. Prior results suggest that the optimal load suspension characteristics are a function of robot morphology and locomotion strategy. A payload suspension system that can be easily adjusted would allow for the accommodation of a variety of these morphologies and locomotion strategies. We have designed a tunable suspension system that will allow for experimentally determining optimal suspension characteristics in a cost-effective manner. The design enables continuous adjustment of the suspension stiffness and damping, so optimal parameters can be determined through hardware experimentation. This hardware experimentation allows for the creation of a numerical model for an oscillating payload’s behavior, which can be compared to simulations. We have completed calculations and design of this hardware, and anticipate seeing that the data collected from its usage will verify the utilization of a haptic testing system in robotics development and allow us to determine methods for calculating the best parameters for elastic payload suspension. This verification of simulated data will allow for further research in developing more efficient methods of payload attachment to legged robots, examination of locomotion when carrying payloads, and design of payload management methods.

Cystic fibrosis (CF) is a genetic disorder affecting the lungs, and chronic polymicrobial lung infections are responsible for decreased life expectancy and poor quality of life of CF patients. Staphylococcus aureus (SA) is a microbe commonly found in the respiratory tract of CF patients, and this organism adapts within the lung environment to establish chronic infections. Among the most common bacterial adaptations is the emergence of mutants known as small colony variants (SCVs). There are multiple subtypes of SCVs that arise from mutations in different metabolic pathways. Recent studies have demonstrated that SCVs are prevalent in the CF respiratory tract, are more difficult to treat with antibiotics, and are associated with worse lung health. SCVs are very difficult to detect in clinical laboratories, thus complicating the selection of appropriate treatment by physicians to improve the health of CF patients. The goal of this study is to determine if SCVs can be more readily detected than with standard culture by using mass spectrometry to identify proteins that distinguish these variants from normal colony S. aureus. Matrix Assisted Laser Desorption/Ionization-Time of Flight (MALDI-TOF) will be used to identify proteins unique to specific SCV subtypes by separating those proteins using ionization and Tandem Mass Spectrometry. This analysis will generate isolate-specific spectra of peaks which will subsequently be compared to each other using Principal Coordinate Analysis (PCoA). We hypothesize this technique will identify differences between proteins produced by each SCV type, which can then be distinguished from normal colony S. aureus, allowing the rapid identification of these variants. As a result, we anticipate the detection of SCV’s will improve, which will help inform physicians to select appropriate treatments to target SCVs.

Cancers are broadly characterized by changes in cell metabolism. Tumor cells typically exhibit functional respiration and inhibition of electron transport chain can impair cancer cell proliferation. However, certain neuroendocrine cancers can arise from loss of function (LOF) mutations in succinate dehydrogenase (SDHx/complex II), which plays a key role in the TCA cycle and in mitochondrial respiration. SDH, which catalyzes the conversion of succinate to fumarate, comprises four subunits: A, B, C and D. LOF mutations in subunits B, C, and D can promote tumorigenesis and mutations in subunit B (SDHB) are particularly associated with malignant and metastatic neoplasms. Interestingly, SDHB impaired cells show an accompanied loss of activity in complex I, implying that unlike the majority of cancer cells, respiration is not essential and may even be antagonistic for SDHB mutant cancer cell proliferation. Indeed, preliminary experiments indicate that inhibition of complex I can restore proliferation to cells treated with an SDH/complex II inhibitor. However, the molecular mechanisms behind this phenomenon are not well understood. We aim to investigate the metabolic mechanisms by which dysfunctional respiration is essential for the proliferation of SDH impaired cells. We hypothesize that inhibition of respiration in these cells can prevent oxidation of NADH to NAD+ at complex I and alter the redox homeostasis in the mitochondria to support proliferation. Specifically, we will test to see if increasing the NADH/NAD+ ratio is the required function of complex I inhibition that rescues cell proliferation in SDH impaired cells. In addition, we will characterize the metabolic consequences of specific alterations SDH, complex I, and mitochondrial redox state. Results from this study should allow us to delineate the importance of metabolic alterations in SDH mutant cancer cells and potentially help identify metabolic vulnerabilities for treatment of SDH impaired cancers.

 Cancerous cells have a modified metabolism that supports their demands for increased proliferation. One of the essential molecules in cancer cell metabolism and proliferation is the amino acid aspartate. Aspartate is not only incorporated into proteins, but is also a substrate for nucleotides and other amino acids, including asparagine. Aspartate availability can constrain tumor growth rate, and the consumption of aspartate to generate downstream products can alter aspartate levels. One gene that draws from the aspartate pool is asparagine synthetase (ASNS). ASNS converts aspartate into asparagine, which is used in the production of proteins, but does not increase cell proliferation. Thus we hypothesize that ASNS expression and activity can affect aspartate levels. With this, we aimed to determine if ASNS expression could alter aspartate availability and change sensitivity to aspartate suppressing therapies. Since cancer cells express ASNS to varying degrees, this project sought to determine if ASNS expression could be used to identify those cancers that are most amenable to aspartate suppression therapies. This research sought to better understand the conditions that determine aspartate levels, and how to exploit those conditions to inhibit tumor growth in association with asparagine synthetase.