Biological load bearing tissues autonomously modulate their properties in response to stimuli from the environment, be it the environment in our bodies or the air around us. Modern implants are utilized as substitutes when these tissues are damaged beyond repair, but one of their greatest limitations is that they can only perform as they are engineered to do. This opens up avenues for research in the development of synthetic materials that can adapt to their environment and self-modulate. Their biologically inspired applications include skin stiffening, tissue reconstruction, bone remodeling, and neural interface interactions, along with textiles, which are included due to their biological compatibility in protecting our bodies. After comparing each application, including the extent in which it has been developed, the leading material in that field, and the areas for improvement that our research interests could fit into, it was determined that this project should focus on the development of a mechanically adaptive material that can perform on par with bone, both in its mechanical properties and in its remodeling capabilities. Polymers were identified as the best material due to their tunable mechanical properties, low cost, and biocompatibility. This material will be a polymeric composite, with a hydrogel matrix and a glass or ceramic filler. Candidate polymers prevalent in tissue engineering were identified as potential hydrogel matrix components. Future work will consist of identifying the filler materials candidates and beginning the formation of the composite.

Recently, soft materials have been under increasing study due to their high flexibility. We are studying a soft material known as liquid crystal elastomers (LCEs). With the ability to change shape when exposed to heat or light, LCEs have found applications in artificial muscles, biomedical devices, and more. These materials are made of liquid crystals (LCs) embedded in the backbone of a polymer, and their LCs can reorient in the direction of an applied stress. Our goal is to experimentally study the mechanical properties of LCEs and further explain their constitutive behavior by focusing on LCEs whose LCs are oriented in the same direction, called monodomain LCEs. We conducted relaxation tests and uniaxial stress-strain measurements at different loading rates on monodomain LCEs that we fabricated with different LC orientations. Effects of stress on LC reorientation were measured using transmission circular polariscopy (TCP), which characterizes the rotation of LCs during deformation. In addition, digital image correlation (DIC) was used to study the shear strain distribution in stretched LCEs. Our results show that the stress-strain relation of LCEs highly depends on loading rate and LC orientation. At low strain rates, the hysteresis in stress-strain curves is small, and LCs can reorient with strain, while at high rates, the hysteresis is large, and there is a lag of LC reorientation. Also, our DIC tests show that LC reorientation causes shear strain within LCEs. These experiments further contribute to the development of theoretical models of LCEs and drive forward LCE technologies.

In the next 30 years, we will see the global population of those 80 years and older will triple. In turn, there will also be an increase in the number of people with age-related diseases. mTOR signaling is the crux of many of these age-related diseases such as Alzheimer’s and Parkinson’s, through inhibiting autophagy, which among other functions removes dysfunctional organelles within the cell. Rapamycin has been shown to alleviate the inhibition of autophagy through negatively acting on TORC1, a major mTOR kinase. Furthermore, rapamycin has shown to improve mitophagy, a specific type of autophagy that removes dysfunctional mitochondria. However, it’s not known how rapamycin affects mitochondrial dynamics. In turn, we hypothesize that rapamycin improves the mitochondrial health through increasing mitochondrial fission, enhancing mitochondrial activity and promoting mitophagy in Drosophila melanogaster. To investigate this, wild-type flies were fed with rapamycin and analyzed its effect on mitochondrial quality. First, we analyzed the effect of rapamycin feeding on pS6k phosphorylation by western blot. As previously describes rapamycin treatment decreases pS6k phosphorylation. Next, we analyzed mitochondrial morphology by immunofluorescence in different tissues including the brain, muscle and gut. Analyzing the effect of rapamycin on mitochondrial dynamics in wild type flies, we can conclude that rapamycin plays a role in mitochondrial quality control. This research will help us better understand the role of rapamycin in lifespan extension and mitochondrial quality control in different model organisms and in humans.

Microglia are resident immune cells of the brain that play an important role responding to brain injury, maintaining cellular communication between neurons and other cells. Microglia undergo cellular and structural changes during development, like an increase in density during postnatal development and refinement in adulthood, but how these changes arise is unknown. Mitochondria may play a critical role in these microglial development changes, such as shape, cell density, and location of these cells. We hypothesize mitochondrial activity can modulate microglia phenotypes, such as shape and structure throughout development. Mitochondria will be immunostained to visualize location in the cell, shape, and mitochondrial mass in microglia during early development. To test this hypothesis, I have begun collecting brain sections from the basal ganglia, focusing on the nucleus accumbens (NAc) and the ventral tegmental area (VTA) of mice ages P8 to 2 months. Then, through confocal microscopy we will obtain high resolution images of mitochondria in microglia. To determine the correlation between mitochondrial state and microglia properties, we performed image analysis using ImageJ. With this analysis, we expect to see an increase in microglial density during the early development of mice (P8) in the VTA and NAc paired with an increase in density of mitochondria.

The gut microbiota regulates host metabolism by interacting with dietary complex carbohydrates that the host cannot digest and producing metabolites such as short chain fatty acids (SCFAs), which can reduce host appetite. It remains unknown whether gut bacterial utilization of complex carbohydrates impacts food preference in mammals. We hypothesize that nutrient preferences of select gut bacteria will affect host dietary preferences via bacterial metabolites acting on feeding-related neural circuits. To study this, we use the commensal bacterium Bacteroides ovatus as a model organism for complex carbohydrate degradation. B. ovatus can selectively metabolize fructans with different linkages: it can metabolize inulin (ID, beta2-1) but not levan (LD, beta2-6). Our preliminary data show that colonization of germ-free mice with B. ovatus modifies host preference for diets with inulin or levan. B. ovatus mice prefer LD over ID. Since B. ovatus cannot metabolize levan, we hypothesize that B. ovatus mice would prefer a ketogenic diet (KD), which contains no fructan, over ID. To test this, we fed B. ovatus mice and germ-free controls KD and ID sequentially for 30 days and assessed their diet preference in a home cage test and fasting-induced food choice task. Here we show that B. ovatus mice consume more KD and prefer KD over ID in a food choice task. Understanding how gut microbiota can influence food preference will contribute to research on altering food choice to prevent metabolic disorders.

A chief feature of heart failure is cardiac fibrosis, a condition in which normally quiescent cardiac fibroblasts become activated. Although the impacts of myocardial fibrosis have been well studied, there is a lack of conclusive research into the cellular mechanisms behind its initiation and progression. Our lab previously analyzed a recently-published single cell RNA sequencing (scRNA-seq) dataset of a transverse aortic constriction (TAC) model of cardiac hypertrophy and found upregulated levels of Nfic among a subcluster of activated fibroblasts. Nfic is a gene that encodes the transcriptional activator and repressor CCAAT-Binding Transcription Factor/Nuclear Factor I C-type (CTF/NF1-C), which is known to be involved in pathways associated with fibrosis. The aim of this study was to examine Nfic’s role as an epigenetic regulator in the development of a heart failure phenotype. In order to elucidate the patterns of Nfic on a genome-wide scale, motif analysis was conducted using HOMER across consecutive weeks of the previously mentioned dataset. A significant presence of Nfic binding sites was detected in genes downregulated between the penultimate and ultimate timepoints of heart failure. The affected genes were found to play angiogenic and proliferative functions, and were uniquely upregulated in the penultimate timepoint and downregulated in the ultimate timepoint as compared to their average expression across the development of heart failure. Primers were designed from a representative selection of these downregulated genes (Emilin2, C1qtnf9, Clec3b) and markers of activated fibroblasts (Col1a1, Acta2) for future use in quantification of their expression levels in Nfic knockdown cells.

Cardiovascular associated diseases (CVADs), like coronary heart disease and fatty liver disease, affect over 17 million people each year. One cause for CVADs is the improper storage of fat by adipose tissue. The buildup of excess fat in organs or blood vessels can present major health problems, such as increased blood pressure and clotting. Therefore, understanding the differences between normal functioning adipose tissue and abnormal functioning adipose tissue is essential for medical prevention and therapies. To this end, we have sequenced single-cell RNA from preadipocytes to establish novel cell-types that are more predisposed to differentiate into unhealthy adipocytes. We have found two distinct sub-groups of preadipocytes with specific marker genes linked to certain CVADs. Further research will be done to characterize these preadipocyte populations and their downstream effects on adipose functionality.

Fragile X syndrome (FXS) is the most common inherited form of mental impairment and autism. In addition to intellectual disability, this neurodevelopmental disorder often presents with atypical sensory processing and tactile defensiveness. Recently, we reported that the Fmr1 knockout (Fmr1-/-) mouse, the most often used animal model for FXS, exhibits similar avoidance responses to repetitive whisker stimulation. This is accompanied with a lack of adaptation of layer (L) 2/3 neurons in the primary somatosensory cortex (S1) to repetitive whisker stimulation and a lower proportion of whisker-responsive neurons from postnatal day 15. Whisker-evoked activity in L2/3 of S1 is shaped by feedforward inhibition from GABAergic parvalbumin (PV) expressing interneurons, and these PV cells are hypofunctional in primary sensory cortices of Fmr1-/- mice. To test if PV cell hypoactivity is associated with tactile defensiveness, we investigated the potential of a novel allosteric modulator of Kv3.1 channels (compound AG00563) to increase PV cell activity in Fmr1-/- mice. We tested the effects of chronic treatment of the compound, using in vivo 2-photon calcium imaging to record neuronal activity. Our results indicate that under acute administration, PV cell firing rose. Both acute and chronic treatments partially rescued the proportion of whisker-responsive pyramidal cells and their neuronal adaptation. These experiments represent the first preclinical studies in a mouse model of autism that investigate the pharmacological manipulation of Kv3.1 channels in PV cells to rescue avoidance behaviors .

One of the most prominent issues in marine transportation is fuel consumption. Water vessels used for long-distance shipping require massive amounts of fuel to operate, and this translates to a steep transportation cost for the customers and an even steeper carbon footprint for the ozone. Therefore, there exists a tremendous financial and environmental motive to develop a method that would lower fuel consumption by decreasing the drag of water vessels. One potential solution lies with superhydrophobic (SHPo) surfaces, which are expected to lower the friction drag of boat hulls without consuming energy. However, despite numerous successful drag reduction experiments in lab facilities, the same SHPo surfaces have rarely seen success in field conditions. Consistent success in open water was obtained only last year by Prof. CJ Kim's lab, using a coupon of SHPo surface made of silicon. To allow for practical applications, the lab has been developing a low-cost, polymer-molded SHPo surface. My project was the development of a preliminary experimental procedure to evaluate the currently available polymer SHPo samples in open water field conditions. The specific tasks included (i) identifying a suitable model boat, (ii) considering how to cover its hull with samples, and (iii) studying how to operate the boat for the experiment on a lake. By comparing the speeds of two identical boats, one covered with the samples and the other not covered, the boat tests would confirm whether polymer SHPo surfaces are effective at reducing drag in turbulent flows of field conditions.

Human-computer interaction (HCI) has advanced the efficacy of a multitude of sectors such as communication and consumerism. However, there exists a gap where most HCI research is conducted to improve quality in industrial aspects rather than personal aspects. Our research extends HCI to improve quality of life by designing and implementing a hand signal response AI into a six degree of freedom (6DoF) robotic arm. We call this our hand signal actuated robotic arm, SARA. An implementation of forward kinematics (FK) and inverse kinematics (IK) in python allows the robotic arm to actuate in response to complex hand signals, made possible via our hand recognition software. This software presents a real-time object-tracking process that recognizes hand signals by finger landmark mapping. A rule classifier distinguishes different variations of raised fingers. To confirm mechanical actuation and limitations, we developed a simulator in MATLAB using a virtual robotic arm that parallels SARA. Our research ultimately produced a design that, when implemented, gives SARA the capability to react to diverse hand signals independently. Qualitative demos conducted with a variety of hand signals validated our research design and implementation. A set of thirty-two hand signals was displayed to SARA that resulted in successful actuation in accordance with the simulator. The application of this design aims to assist individuals with physical limitations, making HCI more personal. The success of implementing a hand signal response AI makes the interaction with a robotic arm intuitive, ultimately expanding the scope of HCI to enhance the human experience.

Purpose: The metabolic processes surrounding adipogenesis have long been studied in their relation to the wound healing cycle and clinically implemented fat grafting. Recently, metabolic manipulation has become an attractive method to induce and sustain adipogenesis. Npas2, a circadian clock regulator gene, has been reported to possess significant metabolic effects relating to adipogenesis. In this study, we investigated the potential effects of Npas2 on adipogenesis of adipose derived stem cells (ASC) in vitro and Npas2 knockout mice in vivo. Methods & Materials: For our in vitro experiment, mouse ASCs (mASCs) were isolated from Npas2 homozygous and heterozygous knockout (KO) mice and wide-type (WT) mice. Cells were cultured with adipogenic medium, while adipogenic genes and lipid accumulation was evaluated. For the in vivo study, WT and homozygous mice were fed different diets: a normal diet (ND) and a high fat diet (HFD) for 12 weeks. Results: In vitro: Npas2 KO ASCs showed significantly higher adipogenic capabilities compared to WT mASCs. In vivo: Npas2 KO mice maintained with ND and HFD, gained significantly more weight during the 12 weeks than WT mice. Blood and liver samples from Npas2 KO mice showed significantly increased fat content. Histological tissue staining revealed larger adipocytes and fattier livers in Npas2 KO mice. Conclusions: Results demonstrate that manipulation of adipogenesis via the suppression of Npas2 yields a noticeable increase in adipogenic activity and body weight, indicating the manipulation of Npas2 may present a fruitful clinical direction for increased production of adipose tissue.