BME Graduate Student Seminar (ZOOM): Simon Leemans and Mehrsa Mehrabi

Friday, April 24, 2020 - 12:00 p.m. to Saturday, April 25, 2020 - 12:55 p.m.
Zoom (link below)
Simon Leemans and Mehrsa Mehrabi

Biomedical engineering graduate students, advised by Distinguished Professor Enrico Gratton and Associate Professor Anna Grosberg.

Seminar via Zoom link: https://uci.zoom.us/j/91872494529

Simon Leemans: Advancing the depth limits of multiphoton microscopy with adaptive optics and DIVER detection

Abstract: Deep tissue multiphoton fluorescence imaging has the potential to advance scientific and clinical discoveries. By noninvasively imaging cells in their native environments, we can leverage the broad range of existing light-based biosensors to better understand signaling and function in complex systems. However, imaging depth is strongly limited by spatial variations in the optical properties throughout biological tissue, causing image blurring and loss of signal. The high laser power required to image deep inside tissue eventually causes top-surface fluorescence, overshadowing the signal and washing out the image, as well as causing photodamage to the sample. To address these challenges, we built the AO DIVER, a multiphoton microscope that combines an improved fluorescence detection mechanism with adaptive optics (AO) to more efficiently focus excitation light into the sample. In highly scattering samples, direct wavefront sensing approaches are impossible at more than a few hundred microns depth due to a rapidly worsening signal-to-noise ratio. To improve optical resolution, we developed software that uses the downhill Simplex algorithm to correct aberrations in ~30 seconds per isoplanatic patch and guides users in performing rapid volumetric phase corrections for high-resolution 3D imaging. With our AO system, we have demonstrated an improvement in the axial resolution of two-photon microscopy by up to 300% in highly scattering samples, far beyond the depth limits of any conventional multiphoton microscope. We have also shown that AO can increase the fluorescence intensity by a factor of five, 400 microns deep into GFP-tagged murine skin, and 1.8 mm deep in formalin-fixed murine YFP-tagged brain tissue.

Mehrsa Mehrabi: In vitro modeling of variable heart diseases due to LMNA mutation via patient iPSC-derived cardiomyocytes

Abstract: Although it is widely acknowledged that heart disease is the number one killer of Americans, what may not be so commonly known is that genetic mutations can cause heart diseases. According to numerous studies, many mutated genes cause heart diseases such as cardiomyopathies and arrhythmias, yet the practical diagnosis and treatment for them are scarce. Lamin A/C gene (LMNA) is one of the genes that can cause dilated cardiomyopathy, arrhythmia and heart failure. This gene codes for proteins, which create a mesh-like layer under the nucleus envelope known as the nuclear lamina. Even though nuclear lamina exists in almost every nucleated cell in the body, there are individuals with LMNA splice site mutation (c.357-2A>G) who mainly have heart problems. The mechanisms by which LMNA mutations cause heart dysfunctions remain a mystery. In this project, human-induced Pluripotent Stem Cells (hiPSCs)-derived cardiomyocytes have been used to develop an in vitro model of the consequences of the mutation on heart function. We demonstrated that it is possible to recapitulate the pathological phenotype in vitro by using patient-specific derived cells and tissue engineering techniques, even though the patients do not exhibit symptoms until later in life. Moreover, this in vitro model of cardiomyocytes tissues can be utilized to correlate  gene profiles, structure and function of the hiPSC-derived cardiomyocytes; thus, elucidating the disease-causing mechanisms.