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Mingjie Dai on furthering our understanding of the molecular basis of life

The Humans of the Wyss series features members of the Wyss community discussing how they think about their work, the influences that help shape them as scientists, and their collaborations at the Wyss Institute and beyond.

In this installment of our Molecular Robotics Edition, we talk to Technology Development Fellow Mingjie Dai, Ph.D., about his work developing methods for detection and visualization of individual protein molecules and how he envisions his research impacting the world.

What drives you?

I am grateful to be surrounded by exceptional intellectual diversity and inspiration, and I’m developing molecular technologies to help further our understanding of the molecular basis of life.

You’re working on single protein detection and visualization, tell us more.

I’m working on developing methods for detection and visualization of individual protein molecules. These are the fundamental, tiny molecular machines that operate and make decisions in our cells, such as controlling cancer cell growth or metastasis. Therefore, it is critical to observe them under the single molecule lens. Exploiting the programmability of DNA molecules as engineer-able molecular machines, we are developing methods for visualizing individual protein molecules inside packed clusters and in the cell. We are also developing fluorescence microscopy based methods that could allow identification of a single protein molecule based on its sequence information.

I am grateful to be surrounded by exceptional intellectual diversity and inspiration…

Mingjie Dai

Share with us some of the challenges you’re facing.

One of the challenges I’m facing is how best to target and detect low-copy proteins. This is partly due to the large dynamic range of human proteome. While some proteins are expressed at tens of millions of copies per cell, others are only at hundreds, or even less. This makes accurate and reliable detection of the less abundant ones extremely difficult. We’re using a combination of biophysical and engineering principles to develop solutions to this problem.

So, how do you envision your research impacting the world?

Detecting and visualizing individual protein molecules is just a first step. Combined with high-throughput methods, we could start to build a systems understanding of the dynamic cellular proteome, and the entire complexity of molecular coordination and interplay. Such quantitative probing of the cellular proteome could help us understand the molecular basis of cellular signaling and control, how cells respond to its environment and make cell fate commitment, and could potentially giving rise to both new molecular diagnostic tools and directions for drug development.

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