How do our cells keep time – or pause it – to shape their physiology? The Aydogan Lab investigates the fundamental principles of biological time control in animal development, metabolism, and disease. We are particularly interested in understanding the utility of time control in tissue homeostasis using animal embryos as a model system. As such, this exciting opportunity involves working along expert scientists at the interface of embryonic biology, metabolism, and biological time control, using techniques ranging from cell and molecular biology to bioinformatics, from advanced super-resolution microscopy to machine learning approaches.

When tissues detect defective cells, they face a dilemma: whether to help repair (cell homeostasis) or decide to eliminate them (cell death). The same quandary occurs at sub-cellular levels too: when cells sense a defect within, they face the difficult choice of either resolving the defect or sacrificing themselves altogether. Decades of work helped reveal cellular mechanisms of homeostasis (e.g., ISR, UPR, DDR, and on) and death (apoptosis, ferroptosis, cell extrusion, and on), yet the molecular justification and decision-making mechanisms that help choose between these two functionally conflicting phenomena are slowly being unearthed. Conflicting indeed, as while the former choice helps a cell survive, the latter benefits the tissue at large by containing the defect locally to avoid its spread. In rarer occasions, even at the face of extreme stressors and damages, cells don’t display hallmarks of death and continue to live on (e.g. polyploidy or suspended animation). How could cells decide between these vital choices?

We rationalize that, at least in part, time is of the essence. When a cellular damage arises, how long could the cell or tissue persist by repairing it? How does a cell decide to slow, speed up or arrest itself to resolve the damages? Does this choice differ when in the cell or tissue’s life cycle the damage occurs? For instance, does it matter that the damage occurs in rapidly dividing cells in a developing tissue versus in post-mitotic cells in an adult organ? Does it make a difference that the same type of damage occurs at different phases of the cell’s division cycle? When and how does a cell or tissue switch from repairing the damages to committing death? Does the cell or tissue age make a difference in the choice of homeostasis versus death? Or, how quickly to go from the former to the latter? All these questions boil down to decision-making mechanisms that rely on measuring the duration of damages or on monitoring the timing and amplitude of their consequences. As such, we conjecture that unravelling the molecular mechanisms and logic of time control in tissue quality maintenance promises the next-generation therapeutic approaches to treating tissue malformations, damages and disorders. In the Aydogan Lab, we use embryonic quality control as a model paradigm to address these questions.

Your role will be to assist an on-going project in this program of the Aydogan to help your day-to-day mentor (graduate student, postdoc or staff associate). You are expected to commit at least 12-15 hours a week with consistent commitment. In turn, you will gain research experience and partake in scholarly endeavors (such as data collection, analysis, interpretation, write up, and potentially even becoming an author on a paper).