Graduate Exam Abstract

Xinran Xu

Ph.D. Preliminary
February 28, 2018, 3:00 pm - 5:30 pm
Odyssey Design Studio in Scott Bioengineering buil
Understanding the murine sperm fertilization process with super-resolution imaging and modeling

Abstract: Tremendous efforts have been put into the study of sperm capacitation signaling pathway. Despite the accurate temporal points to induce the
capacitation event, various proteins are also spatially regulated and confined to ensure its occurrence. In the last few decades, the revolutionary
development of fluorescent proteins and other genetically encoded fluorescent labels have allowed us to visualize specific proteins in both fixed
and live cells. However, the diffraction limited resolution of conventional fluorescence microscopy hinders us from progressing, which
approximately yields a PSF with a lateral size of 250 nm and axial size of 500nm. With these being said, the nanoscale sub-cellular architectures
of proteins, one of key ingredients to determine the mechanical properties of cells, are still lacking. Meanwhile, a stochastic model that integrates
the key players involved in the capacitation process is also missing in the field for quantitative understanding as well as predicting the molecule
states and concentration fluctuations. Here, We employed super-resolution imaging technique to resolve the ultrastructure of actin cytoskeleton
and quantify the structure to further understand the connection of the structure with the emergence of hyperactivation. On top of that, we will
have also identified an unconfirmed kinase with super-resolution imaging along with biochemical assays. Meanwhile, the capacitation-mediating
protein PKA has also been imaged under the condition with or without inhibitory drug during the evolution of capacitation to investigate how the
spatial change affects the process. Furthermore, a quantitative model driven by the different titration data will be developed and validated to
eventually build a predictive model for the fate of proteins during this process.

Adviser: Diego Krapf
Co-Adviser: N.A
Non-ECE Member: Michael Tamkun, Biomedical Science
Member 3: Ali Pezeshki, Electrical and Computer Engineering
Addional Members: Brian Munsky, Chemical and Biological Engineering

[1].Alvau, Antonio, Maria Agustina Battistone, Maria Gracia Gervasi, Felipe A. Navarrete, Xinran Xu, Claudia Sánchez-Cárdenas, Jose Luis De la Vega-Beltran et al. "The tyrosine kinase FER is responsible for the capacitation-associated increase in tyrosine phosphorylation in murine sperm." Development 143, no. 13 (2016): 2325-2333.
[2].Krapf, Diego, Enzo Marinari, Ralf Metzler, Gleb Oshanin, Xinran Xu, and Alessio Squarcini. "Power spectral density of a single Brownian trajectory: what one can and cannot learn from it." New Journal of Physics (2018).

Program of Study: