Events for 04/24/2025 from all calendars

Mathematical Biology Seminar

Time: 4:00PM - 4:50PM

Location: BLOC 306

Speaker: Razeen Shaikh, Texas A&M University (Chemical Engineering)

Title: Optimal performance objectives in the highly conserved bone morphogenetic protein signaling pathway

Abstract: Throughout development, complex networks of cell signaling pathways drive cellular decision-making across different tissues and contexts. The transforming growth factor β (TGF-β) pathways, including the BMP/Smad pathway, play crucial roles in determining cellular responses. However, as the Smad pathway is used reiteratively throughout the life cycle of all animals, its systems-level behavior varies from one species or context to another, despite protein sequences and pathway connectivity remaining almost perfectly conserved. For instance, the Smad pathway has the flexibility to enact a rapid response in some cell types, but a high-noise-filtering response in others. Our work examines how the BMP-Smad pathway balances trade-offs among three such systems-level behaviors, or “Performance Objectives (POs)”: response speed, noise amplification, and the sensitivity of pathway output to receptor input. Using a mathematical model of the Smad pathway fit to human cell data, we show that varying non-conserved parameters (NCPs), such as protein concentrations, the Smad pathway can be tuned to emphasize any of the three POs and that the concentration of nuclear phosphatase has the greatest effect on tuning the POs. However, due to competition among the POs, the pathway cannot simultaneously optimize all three, but at best must balance trade-offs among the POs. We applied the multi-objective optimization concept of the Pareto Front, a widely used concept in economics, to identify optimal trade-offs among the various requirements. We show that the BMP pathway efficiently balances competing POs across species and is largely Pareto optimal. Finally, we validate the relationship between relative phosphatase levels and approximate BMP signaling response time for three biological systems: Human Aorta, Zebrafish embryo and Drosophila embryo. Our findings reveal that varying the concentration of NCPs allows the Smad signaling pathway to generate a diverse range of POs. This insight identifies how signaling pathways can be optim