Cells use a protein called Notch as a receiver for signals that tell them to multiply, change behaviour, or die—but no one knows how the same receiver can trigger such different outcomes. This matters because faulty Notch signalling drives several types of cancer and other diseases. The researchers are working out the "language" of Notch messages, using fruit flies as a simpler model. Because around 80% of human disease genes have counterparts in flies, findings should translate to people. If the team succeeds, they will identify molecular "signatures" that show when Notch is working inappropriately in a patient. That could guide treatment choices—for example, flagging which cancers might respond to existing drugs or require different approaches. The signatures could also reveal new targets for drug development. This is fundamental science: the team is decoding a core communication system in cells, not testing a therapy. But similar work on Notch—first discovered in flies—has already led to cancer drugs in clinical use. Understanding the signal's grammar could unlock the next generation of treatments.
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The human body is composed of millions of cells which have to be assembled and maintained correctly. For this complex assembly process to happen, the cells need to communicate with each other. They do so via special types of signals. One such signal uses a protein called Notch as its receiver. Messages sent through Notch can make cells proliferate or change their behaviours, and sometimes even die. What we don?t understand is how Notch can communicate such different messages at different times. This is of major importance because we now know that inappropriate activity of Notch is responsible for several types of cancers and is linked to other disease too. The goal of our work is to understand the language of the different messages that Notch sends at different times and to identify particular ?signatures? that will be helpful in clinical situations to show whether Notch is working inappropriately. If it is, this may influence what treatments should be provided. In addition, the ?letters? within a signature could give us good clues about ways to develop new drugs for particular cancers in future. We do most of our experiments using the fruitfly, which gives us a simpler model to decode these different messages. Because there are very big similarities between the ways cells work in flies and people (Notch was first found in fly studies and ~80% of disease causing genes can be found in flies) we are confident that the fly experiments will give us a route to important tools for use in the clinic.
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