Total Recall
The project is called Total Recall "Learn–Recall–Forget: Causal Circuits of Starvation Memory for Population Coherence in Homeostasis and Development". It was funded through the "Toppforskere" programme from the Research Council of Norway, which supports research teams with the potential to become world-leading in their field.
The team is led by Jorrit Enserink from the Department of Biosciences and Oslo University Hospital, and Helene Knævelsrud from the University of Oslo. In addition to Enserink and Knævelsrud, the Total Recall team includes Pierre Chymkowitch and Eivind Valen from the Department of Biosciences and Manuela Zucknick from the Institute of Basic Medical Sciences. They bring together expertise in molecular biology, genetics, developmental biology, and statistics.
Cellular memory of nutrient stress
Every living organism faces periods when food is scarce. When that happens, cells switch from growing to recycling, breaking down their own components to survive. This recycling process, known as autophagy, must be tightly coordinated across millions of cells. If some cells respond too slowly or not at all, tissues can be damaged and development can go awry.
The Total Recall team has made a remarkable observation: Cells don't simply react to starvation as if each episode were new, but they learn from experience. After a first bout of starvation, cells activate their survival programme faster and more synchronously the next time around, in a manner strikingly similar to how repeated studying strengthens human memory. Longer initial exposure produces stronger recall, similar to the well-known benefit of spaced repetition in learning by the human brain.
This cellular memory may be far more important than previously recognised. In tissues and developing organisms, the ability of cells to mount a coordinated, well-timed response to nutrient stress is critical for healthy growth and organ formation. Memory could be what keeps millions of individual cells acting in concert rather than drifting into disorganised, potentially harmful responses. When cellular memory fails, or when cells cannot properly forget outdated information and regain flexibility, the consequences may include developmental defects, impaired tissue function, and disease.
Yet despite its significance, cellular memory of nutrient stress remains poorly understood. It is not known which molecules store these memories, how they are recalled, or how cells eventually erase them to stay adaptable. Total Recall aims to answer all three questions. The research begins in yeast, where individual cells can be tracked with precision, and extends into fruit flies and zebrafish to test whether the same memory principles operate in developing animal tissues.