Monash scientists crack cholesterol code with new drug target

By Our Reporter
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Cholesterol, while vital to cellular health, can lead to problems if not properly regulated. Unchecked cholesterol levels are often linked to tumours and neurological issues

Researchers from Monash University have made a crucial breakthrough that could pave the way for new treatments in cancer and neurological disorders. At the centre of their discovery is the protein LYCHOS, which has the unique ability to sense cholesterol levels and regulate cell growth. This research could transform how we approach diseases caused by abnormal cell growth.

Cholesterol, while vital to cellular health, can lead to problems if not properly regulated. Unchecked cholesterol levels are often linked to tumours and neurological issues. The Monash research team, led by Associate Professors Andrew Ellisdon and Michelle Halls, revealed the structure of LYCHOS for the first time, thanks to advanced cryo-electron microscopy. This cutting-edge technique allowed the team to capture a highly detailed image of the protein’s three-dimensional structure.

What makes LYCHOS truly remarkable is its unusual composition, which shares characteristics with both plant transporters and G protein-coupled receptors (GPCRs), a type of protein commonly targeted by pharmaceuticals. This dual nature of LYCHOS as a cholesterol sensor could have significant implications for drug development. The team believes that targeting LYCHOS could help control the unchecked cell growth that often leads to diseases like cancer.

LYCHOS is not just any protein—it plays a key role in activating mTORC1, a complex involved in regulating cell metabolism and growth. With mTORC1 implicated in many serious health conditions, LYCHOS represents a promising avenue for treatment development. Drugs aimed at modulating its activity could provide much-needed precision in tackling diseases driven by cholesterol imbalance.

The team’s work is already sparking excitement in the field of drug discovery. The discovery of LYCHOS’ hybrid structure, which combines a plant-like transporter and a GPCR, is unprecedented in human biology. This unusual combination allows LYCHOS to detect cholesterol and control cell growth in a way that has never been observed before.

By deepening their understanding of LYCHOS, researchers hope to develop targeted treatments for conditions like cancer and metabolic disorders. It’s not just a victory for the Monash team; this breakthrough could have far-reaching impacts on how we treat some of the most challenging diseases.


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