Sperm selection is a critical problem in assisted reproduction. In an effort to understand the elusive qualities that predict sperm 'fitness', we are studying the complex integration of 'sensory' and metabolic systems in the regulation of capacitation (the process of gaining fertility competence). We are especially interested in how properties of regulation scale from individual sperm cells to cell collectives and how local microenvironmental conditions in vitro modulate these processes. We are developing methods for high-speed fluorescence imaging, potentiometry, spectral flow cytometry, and multidimensional culture arrays. Our ultimate objective is to analyze how sperm subpopulations diverge and evolve throughout the post-ejaculatory lifespan. Image: Temporal Coded Image of Motile Mouse Spermatozoa.

Sperm cells fundamentally do two things: 1) move in a manner that increases probability of contact with an egg, and 2) coordinate exposure of surface recognition molecules during fertilization to facilitate specific binding with the egg. Both of these processes are energy and material intensive and require exact coordination of metabolism and sensory/control processes. In these projects, we are modeling the metabolic subsystems that support sensory control of capacitive change and motility in mammalian sperm using high resolution respirometry, fluorometry, analyte detection, and mathematical modeling. Our primary goal is to understand the common biochemical structures/subsystems that underlie sperm energy transduction.  Image: Fluorescent mitochondria of an epidydimal mouse spermatozoa.

Sperm selection for in vitro fertilization and cryopreservation will benefit from an appreciation of the importance of large numbers and phenotypic heterogeneity in sperm samples. To test microenvironmental influences, a tractable system must be developed to allow sperm cells to be deposited in a defined space (as in insemination) and allowed to disperse in accordance with their phenotypic properties. These projects accompany our theoretical work on the theory and consequences of sperm selection. We are developing cost effective microfluidics platforms to facilitate empirical testing of our theoretical predictions that allow us to precisely control the shape and fluid properties of the local environment during sperm capacitation. Image: Start/stop actuatable flow of fluorescent beads in our low-cost microfluidics system. 

The 20th century view of biology was heavily influenced by an explosion of theoretical and scientific knowledge about machine technologies. Much of this machine-like or 'mechanistic' thinking has influenced our explanations of cell biology. In the 21st century, our worldview has shifted to include questions about  the nature of information processing and complexity. Are cells truly 'machines' that consist of finite parts, or are they better understood as emergent processes that exhibit the mysterious property of agency? In these projects, we are developing agent-based modeling of artificial living systems (Alife). These computational models allow us to leverage existing datasets and explore how physiological properties emerge from the collective interactions of cells with their local micro-environments. We are also developing methods to test our model predictions directly using experimentally tractable systems including live-cell imaging in custom microfluidics devices. Image: Agent-Based Model of Sperm Population Dynamics.