Protein biochemist Sascha Nicklisch likens the cells in our bodies to bustling nightclubs. Like patrons entering and exiting an establishment, a constant flow of biochemical interactions via proteins occurs, ensuring the functions necessary to sustain life.
But this system can be exploited by environmental toxicants. While our cell’s defense system — known as the cellular defensome — is pretty adept at identifying and rejecting toxicants, some chemicals slip through.
Take the pesticide DDT, for example, which has been linked to cancer, reproductive and neurological issues. Despite being banned from U.S. agricultural uses in 1972, DDT is a persistent organic pollutant. Evidence of it can still be found in our seafood sources, thus having an avenue to get into our bodies through what we eat.
“The big question for me, as a protein biochemist, is, why do these chemicals still get into our body?” said Nicklisch. “Why are they not pumped out?”
Nicklisch, an assistant professor in the Department of Environmental Toxicology at UC Davis, was the March 2026 speaker at the Davis Science Café, an event series hosted by Professor of Chemistry Jared Shaw and the Department of Chemistry.
Nicklisch’s talk focused on his lab’s research on the protein multidrug resistance 1, or MDR1, which functions as a guard, allowing cellular access to some chemicals while blocking out others. Nicklisch affectionately refers to MDR1 as the “molecular bouncers” of the cell.
“We can find [MDR1] in all living organisms, from bacteria to humans,” he said, noting that the protein can recognize and pump out over 600 chemicals, including synthetic compounds.
“We have a very potent, very capable protein in our body,” he added. “What do these chemicals do that they evade, that they avoid, this protein?”
The strategy employed by chemicals like DDT may sound familiar to those who have snuck past a bouncer at a nightclub.
It’s all a game of distraction
Nicklisch revealed that DDT acts like a distractor in the molecular environment. It’s what’s known as a transporter interfering chemical, or TIC. In essence, TICs, such as DDT, bind to transporter proteins, such as MDR1, and disrupt their functionality.
“It binds exactly where it should bind, where a substrate should bind, but it just doesn’t get off,” Nicklisch said.
Fastened to the MDR1 protein, DDT opens the molecular door to a cell’s interior environment and keeps it open, allowing access to other chemicals that would usually get kicked out by MDR1.
“You’re not only distracting the bouncer from yourself…but also all your buddies,” Nicklisch said.
Nicklisch and his research colleagues have seen this molecular interaction up close thanks to a high-resolution imaging technique called cryogenic electron microscopy.
“They block the function of pumping, of protecting our cells against harmful chemicals, and that leads to the accumulation of these chemicals in food organisms,” he added.
A legacy of pollutants
One food organism Nicklisch and his team have extensively studied is yellowfin tuna, which accounts for roughly 30% of the global tuna catch.
“We also chose that fish, not only because it’s a third of the global catch…but also, this is one of the few tuna species that kind of stays local,” he said. “It kind of stays along the warm waters of the equator…which allows you to create a local snapshot of chemical pollution in a fish that relates to where you catch the fish.”
In a 2017 study, Nicklisch and colleagues sampled 117 yellowfin tuna from 12 different locations across the globe. The team found that fish caught in more industrialized locations, including the northeast Atlantic Ocean, the northeast Pacific Ocean and the Gulf of Mexico, contained higher levels of persistent organic pollutants, including DDT and other TICs, than fish caught in more untouched areas. In a related study, the researchers looked at the mercury content in the same fish and similarly found that catch site also mattered.
The presence of these chemicals in modern fish are likely remnants of our species’ past environmental pollution. For example, from the 1940s to 1972, an area in the northeast Pacific Ocean, off the coast of Los Angeles, was a known dumpsite for industrial waste, including DDT chemicals.
“[These chemicals] don’t degrade well in the environment,” Nicklisch said.
What’s more, the molecular machinery that TICs, such as DDT, exploit in fish is conserved across species, including humans.
“This is how these compounds, these chemicals, accumulate, or we sometimes say bio-magnify,” Nicklisch said.
While more research is being done to understand if the levels of TICs present in modern yellowfin tuna are harmful to humans, Nicklisch said his lab’s functional research will help elucidate exactly how harmful chemicals bypass our cell’s defense system. That research could then be used to potentially carve a path towards protection.
But the science pushes beyond food safety.
“We also want to understand how blocking of these MDR proteins by environmental chemicals could affect how our body deals with medications that are also pumped/cleared out by these transporters,” he said. “Unintended exposure to TICs in our food could block these proteins and inadvertently lead to an overdose of a given medicine that was supposed to be pumped out at a constant rate by these proteins.”
The Davis Science Café is held every second Wednesday of the month. Learn more about the Davis Science Café.
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