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Summer 2022

Project Background

This project uses human brain organoids as a tool to study and treat the neural bases of neurological disorders, and epilepsy in particular. This is a cutting-edge project; the engaged student will be one of the few people in the world who will be working with these brains and record and manipulate their electrophysiological activity. The project is developed to the point where the student can begin to record from the organoids immediately.

Student Role

The student will determine the electrophysiological mechanisms that underlie epilepsy in the human brain. Specifically, the student will compare the electrophysiological activity of brain organoids from healthy subjects to organoids derived from the genome of epileptic patients.
The student will introduce specific drugs that interact with specific ion channels, and determine which agent is most effective to quench epilepsy in the brain tissue of the given patient.
This approach opens a path to personalized treatments of epilepsy, and may evolve into large collaborations with the industry.

Student Learning Outcomes and Benefits

The project is highly interdisciplinary. It combines the study of developmental biology (growing brain tissue), engineering (implanting and recording from individual neurons), and science (the mechanisms underlying spilepsy). It allows the student to synthesize her/his knowledge of multiple domains or classes and put them into practical use. It also enables the student to further her/his experience with data analysis. This project is highly attractive and the student will present the results at a national conference. This shall further her/his sense of accomplishment, excitement about the project, and her/his enthusiasm for research and science.

Regarding specific learning outcomes, the student will

  1. Learn about a new model of the human brain---human brain organoids grown from induced pluripotent stem cells.
  2. Learn how to record electrophysiological activity from the organoids using implanted electrode arrays.
  3. Learn how to analyze the signal.
  4. Learn how to visualize epileptic versus normal brain activity.
  5. Learn how to stop epileptic activity with appropriate agents.

Jan Kubanek

Assistant Professor

Targeted Noninvasive Treatments of the Nervous System
Mental and neurological disorders are the world's leading cause of disability. Systemic treatments with drugs are often ineffective and can have significant side effects such as being highly addictive. Our lab develops minimally invasive methods to diagnose and treat brain disorders in a targeted manner, at their neural source.

Ongoing work

Remote control of neuronal activity

The ability to control cellular excitability remotely has many implications for basic science and clinical treatments. One form of energy, sonic waves of high frequency (ultrasound), is particularly well suited for this purpose as it can be focused into confined targets deep in biological tissues. We investigate the biophysical interactions of ultrasound with tissues. We assess the efficacy and safety of the interactions in animal and human models.

Remotely-controlled drug release at a specific target

The ability to deliver a drug selectively at a specific location within the body would revolutionize medicine. Building on the pioneering approach of Natalya Rapoport (University of Utah), we use ultrasound to release drugs from specifically designed nanoparticle carriers. We optimize the efficacy and safety of the approach in large animals.

This work will enable us to move beyond prescribing systemic drugs by specifically modulating the aberrant neural circuit in a given individual. At the basic science level, the ability to modulate (and in particular, suppress) neural circuits noninvasively and thereby systematically will lead to new, causal studies of how individual brain circuits are involved in specific behaviors in humans.

As a Principal Investigator, I will engage the student in the following activities:

  1. Guide the student in performing the experiments while helping her/him to see the big picture.
  2. Show the student how to analyze the signals recorded from the brains, and allow her/him to write her/his own scripts that improve our current simple analyses.
  3. Allow the student to present results and receive feedback in our weekly lab meetings.
  4. Regularly talk with the student about her/his teaching/mentoring experience and how it can be made even more effective.
  5. Regularly discuss with the student her/his future plans and potentially serve as her/his senior thesis mentor if the student agrees so.