David Lawrence, PhD — What Happens in the Cell Stays in the Cell
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David Lawrence, PhD — What Happens in the Cell Stays in the Cell
What Happens in the Cell Stays in the Cell
Lawrence’s research focuses on the biochemical processes of the cell. Traditionally, scientists study these processes by cracking open the cell, purifying its enzymes, and observing their reactions in an artificial environment in a cuvette. Lawrence’s approach, however, aims to study the enzymes without removing them from the cell. To do that, one must overcome a series of hurdles.
“Biochemical sensors are an exciting way to look inside a cell and visualize the chemistry as it’s taking place,” Lawrence says. “However, one needs to design these sensors, synthesize them, and figure out how to deliver them into cells. The sensor has to be selective for a particular chemical transformation. The sensor then needs to report back to the investigator what’s actually going on inside this little bag that contains thousands of different proteins, nucleic acids, and carbohydrates. Sometimes, you don’t want the sensor working until the cell reaches a particular stage. The latter can be a real problem, because once a probe is placed inside a cell, you lose control over that probe.”
Lawrence has devised a way for researchers to retain some of that control, even after the probe has entered the cell. His group has developed light-activated sensors, inhibitors, and enzymes. These molecules are inert when they enter the cell, and scientists can switch them on by exposing them to varying wavelengths of light.
“The beauty of the light is that we have control over not only when we switch the sensor or enzyme on, but where we switch it on inside the cell as well,” Lawrence says. “So if we want to activate an enzyme near the cell membrane, we can do that and see how the cell responds. This allows us to correlate the activities of a particular protein with the subsequent cellular response.”
The idea of light-activated molecules isn’t new—it was developed in the 1970s. However, the approach had been applied generally to only in vitro systems. More recently, Lawrence and other researchers have recognized the usefulness of the method for cell-based studies.
While part of Lawrence’s research focuses on understanding the chemistry of the cell, other aspects of his work have potential therapeutic applications. For instance, his group has developed molecules that can activate the insulin and leptin signaling pathways, which could be useful for treating diabetes and obesity. In addition, his group has developed other agents that may prove useful for treating various forms or cancer as well as certain rare genetic disorders.
Lawrence has also used light-activated molecules to control gene expression to study cancer development in cells. Commonly, in order to study carcinogenesis in animals, researchers have to inject cancerous cells into healthy subjects or create a transgenic animal that is designed to develop cancer as it grows up.
Lawrence says neither of those approaches simulates the environment in which cancer typically develops in humans. He is working on technology that would feed a molecule to healthy animals. The molecule remains inert until researchers trigger it with light, at which point it switches on the gene of interest in cells in the affected area, allowing researchers to observe the consequences. The procedure has been successful in experiments with cell cultures, and Lawrence is collaborating with two former colleagues at the Albert Einstein College of Medicine on the next step.