IBSC-BME PhD Preliminary Examination Announcement for Worapat Sawatwong (D. Little and D. Chan, co-advisors) Everyone is invited to attend the public presentation beginning at 10:00 AM. Research title: Influences on Bone Mechanosensitivity: Mechanical Load Distribution History and Alterations in the Gut-Bone Axis Date: Wednesday, May 15, 2024 Time: 10.00 AM Place: LYNN 1192 Thesis Committee members: Dr. Dianne Little (co-chair, BMS) Dr. Deva Chan (co-chair, BME) Dr. Timothy Lescun (VCS) Dr. Andrew Brightman (BME) Dr. Glen Niebur (University of Notre Dame) Abstract: Osteoporosis is a bone disease that affects over 20% of the global elderly population. It is characterized by reduced bone mass and strength, leading to increased fracture susceptibility due to diminished responsiveness to mechanical stimuli. Understanding how bones sense and respond these mechanical signals is crucial, as it directly relates to osteoporosis severity and fracture risk. There remains a critical need to identify the key factors influencing bone mechanosensation to develop effective interventions for osteoporosis patients. Tissue-level mechanical strain directs bone adaptation. Non-physiological strain distributions can induce bone formation even under normal strain levels, highlighting the significant impact of strain distribution on bone mechanosensitivity. Physiological strain is influenced by daily locomotion patterns, which vary across species. For instance, sprawling locomotion in reptiles with distinct stances and load distributions from quadrupedal mammals, may establish novel bone mechanosensitivity pathways. Additionally, systemic perturbations like disrupted gut microbiome (GM) diversity - dysbiosis, alter bone homeostasis through inflammatory changes, affecting bone quality. Antibiotic use disrupts long-term GM diversity and may influence bone adaptation and mechanosensation, while exercise may offer restoration. However, specific responses of osteocytes to different strain modes, the impact of locomotion stance on bone mechanosensitivity, and the interplay between GM dysbiosis and exercise on bone health remain unclear. We hypothesize that these mechanical load experience and systemic interference impact bone metabolism. Aim 1 will assess the effects at the level of gene expression of different strain distribution patterns during loading using two external mouse tibia loading models on bone cells. Aim 2 will investigate bone remodeling responses in sprawling hindlimb gait quadrupeds using iguana models. Aim 3 will study the interplay between antibiotic-induced GM dysbiosis and treadmill exercise on long-term bone homeostasis using mouse forelimb bones. Understanding the factors influencing changes in bone mechanosensation is essential for developing new drug targets and mechanical stimulation for osteoporosis patients. Completion of this project will help me develop the skills necessary for my long-term goal of becoming an independent researcher in musculoskeletal biology, osteoporotic disease, and sport sciences.