Biotechnology at CCSF

Carmen Lai

"As graduation inched closer, I began to doubt my ability to successfully transition from being a student to a full-time working professional, especially in a laboratory setting. It bore no significance whether I graduated with a BS in Biochemistry & Molecular Biology or had worked in a marine biology lab for two years in addition to my academic lab curricula—I lacked the qualifying work experience detailed in many entry level job listings for the private sector at the time.

To address this, I researched where I might gain more hands-on lab experience when I returned home to San Francisco from college still unable to sustain a living with the jobs available to me. This was when I discovered the Biotechnology Program at CCSF was offering exactly what I wanted, more lab work experience on cutting-edge research projects.

The Biotechnology curriculum allowed me to further reinforce my conceptual knowledge in biosciences and apply this knowledge in the lab work setting. The true testament to my competency working in bioscientific research has been my success in the Stem Cell Technology Certificate program and as a CIRM intern in the McDevitt Lab!"

Stem Cell Internship: McDevitt Lab, Gladstone Institutes

Project Title: Engineering a 3D Human Model of the Neuromuscular Circuit

Abstract: Human stem cell assays hold great promise for investigating the molecular, cellular and circuit development and disease progression in a controlled and systematic manner. Most human in vitro models, however, are 2-dimensional cultures (or cocultures) of a single cellular phenotype, greatly underrepresenting the complex architecture of native tissues. Advances in organoid (3D) engineering have increased feasibility for 3D tissue formation which may serve as physiologically relevant platforms for various applications including developmental and disease modeling, and drug discovery. Here we describe the methods necessary for engineering a human model of the neuromuscular circuit comprised of interneurons (INs), motoneurons (MNs), and muscle cells. Specific ventral interneuronal populations were derived from optogenetic (channel-rhodopsin2) human induced pluripotent stem cells (hiPSCs), while MNs were derived from doxycycline-inducible hiPSCs (NEUROG2, ISL1, LHX3). Muscle cells were generated using primary human myoblasts. IN-MN connectivity was assessed using multielectrode array (MEA) by stimulating optogenetic INs while recording from MNs plated on top of the electrodes. The three cell types were then seeded into compartmentalized bioreactors which separate the cell types allowing for axonal extension from the neuronal cells to the muscle tissue enabling us to measure the contractility of the seeded muscle tissues. By combining 3D tissue engineering, optogenetics, microfabrication, and optoelectronics, we created a novel platform for precise investigation of development and degeneration of the human neuromuscular circuit, and posit its future utility for modeling progressive human neuromuscular diseases.

Carmen Lai - Engineering a 3D Human Model of the Neuromuscular Circuit - CCSF CIRM Intern 2021-22.pdf

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