Physics Graduate Seminar Presented by Luke Ali, graduate student (Advisor: Prof. Jan Scrimgeour)
Modeling Hyaluronan Synthesis by Non-Processive Enzymes
Hyaluronan (HA) is a long polymer chain composed of glucuronic acid and N-acetylglucosamine sugars which repeat in an alternating fashion. It is produced naturally by virtually all cells in vertebrates but presents primarily in the extracellular matrix. Its function is strongly dependent on polymer size. In humans, HA promotes tissue repair by allowing increased cell motility, and supports the skeletal system by providing joint lubrication. Recent publications have shown that HA also plays a role in the survival of cancer cells, having both pro-tumorigenic and tumour suppression effects.
While HA has become very important in therapeutic relief, its cost is a significant issue: 1kg of 2500 kDa HA can cost upwards of $20,000. One approach to HA synthesis is via in vitro reactions catalysed by purified HA synthesis enzymes. In this talk, we examine one such reaction that uses the hyaluronan synthase enzyme from the bacterium P. Multocida, which has been shown to enable tightly controlled polymer synthesis.
We first develop a kinetic model for the synthesis reaction, then using computer simulations we demonstrate an excellent qualitative match with previous experimental findings. The model reproduces many of the detailed behaviours observed in experimental reactions on short and long timescales. Our hope is that a detailed model of the synthesis reaction will lead to further reaction optimization and add to our knowledge of HA synthases behaviour generally.
Friday, December 6th 2024 3:30pm SC 344