Research
Minerva Fast Track Group: Guhathakurta Lab
We combine human stem cell derived models of neural differentiation with multi-omic, biochemical, and live-imaging approaches to dissect signaling events across subcellular compartments in real time. This allows us to trace how metabolic and hormonal cues are sensed, transduced, and translated into lasting changes in cell identity and function. Spanning early neurodevelopmental decisions through to ageing-associated decline.
Our projects address complementary layers of this problem, from the biochemistry of individual metabolite-enzyme interactions to systems-level analysis of neuron-glia crosstalk, reflecting our view that cell fate control cannot be understood by studying epigenetic, metabolic, or hormonal regulation in isolation.
Project 1: Epigenetic and metabolic crosstalk during early brain development
The human brain enables higher cognitive functions, complex information processing, and flexible behaviour. In neurodevelopmental disorders such as ADHD, autism, and dyslexia, these abilities can be disrupted, making everyday life more challenging. Many of these disorders are linked to altered early brain development, where most neurodevelopmental processes take place. A key event during this stage is neural stem cell fate specification, when progenitor cells decide whether to keep dividing or differentiate into neurons, oligodendrocytes, or astrocytes.
We are particularly interested in understanding how metabolism and epigenetics interact to regulate these fate decisions. Metabolism is not only a source of energy but also a driver of epigenetic state, influencing gene expression during development. Although genetic studies have linked mitochondrial and metabolic genes to neurodevelopmental disorders, these associations do not yet explain the underlying mechanisms.
Our lab is interested in investigating how metabolic and mitochondrial pathways shape epigenetic regulation during neurogenesis. By understanding this interplay, we aim to uncover fundamental principles of brain development and identify mechanisms that may be disrupted in neurodevelopmental disorders.
Prerna Swarnim is the PhD student leading this project, supported by IMPRS.
Project 2: Estrogen-dependent mechanisms of brain cell resilience
Estrogen signaling influences brain development, cellular metabolism, and stress adaptation, yet the mechanisms by which it shapes protective cell states in the human brain are still not fully understood. This project investigates how estrogen-dependent pathways regulate chromatin state, mitochondrial function, and stress resilience in human neural and glial cells.
Using human stem-cell-derived brain models, we aim to define how hormonal cues influence cell identity, metabolic wiring, and neuron-glia communication. By integrating molecular and functional readouts, the project seeks to uncover how estrogen-regulated mechanisms contribute to brain resilience, and how their disruption may increase vulnerability during ageing and neurodegenerative disease.
This project is led by Maria José Pérez J. PhD, and is supported by the CIBSS and Klaus Tschira Boost Fund.