Madison Reporter

University of Wisconsin–Madison biochemists have developed a method to enable rapid detection of harmful substances in the body and environment. This advancement could assist first responders, environmental monitoring groups, and individuals in identifying health-relevant substances quickly.

The research team has focused on small molecules that interact with proteins, which can either support or hinder biological processes. While some small molecules like vitamins are beneficial, others such as opioids can be toxic. Identifying these molecules is crucial for emergency medical treatments and environmental safety.

Currently, detecting small molecules requires expensive lab tests that are time-consuming. In emergencies like drug overdoses, delays in testing can affect treatment outcomes. An efficient on-site test kit could improve emergency responses and home health monitoring.

“Small molecules are pervasive in all of biology,” said Vatsan Raman, a UW–Madison biochemistry professor. “Nature is really good at creating proteins that bind to small molecules with exquisite specificity.”

Raman's team aimed to design a system where engineered proteins detect specific small molecules by initiating a biochemical alert system when they encounter them. However, engineering such proteins involves extensive testing to find the right fit.

To address this challenge, researchers developed Sensor-seq—a method allowing simultaneous screening of numerous protein mutations to identify those binding effectively with target molecules. These proteins can be modified to signal visually when a molecule is detected.

The team tested Sensor-seq using naltrexone, an opioid mimic drug. They identified protein mutations that sensed naltrexone and created a biosensor that glows green upon interaction with it.

Their findings were published in Nature Communications and showed promising results as naltrexone induced visible green fluorescence.

Researchers are now building computer models to streamline protein matching for other relevant small molecules affecting human and environmental health.

“What we learn from these large datasets will make our process more effective and efficient,” said Raman. “My goal is that if you tell me what molecule you want to sense, we should be able to give you a protein biosensor for that molecule in just a couple of weeks.”

The project includes potential military applications through collaboration with the Air Force Research Laboratory and support from the U.S Army.

“We’re excited about these results from Professor Raman and his research team,” stated Stephanie McElhinny from the Army Research Office. “The DEVCOM Chemical Biological Center is exploring the potential of the Sensor-seq biosensor discovery approach.”

Raman envisions broad applications for this technology including field tests for pollutants in water sources and at-home health indicators tracking.

“We started with naltrexone because there’s a strong need for low-cost ways to detect opioid use,” explains Raman. “But...we can create a biosensor for any small molecule."

This research received support from United States Army Research Office Grants W911NF20C0005 and W911NF1710043.