Research Areas
Cells are extraordinarily complex biological systems, governed by intricate chemical interactions between DNA, RNA, proteins, and a diverse array of small organic and inorganic molecules. While studying the entire cell as a unified system remains beyond current capabilities, we can make meaningful progress by identifying key molecular processes, with well-defined, experimentally tractable features that serve as “pieces of the puzzle.” By dissecting these components at the molecular level, we gain foundational insights that can be integrated to build a deeper understanding of cellular function as a whole.
Our scientists are driven by fundamental questions at the heart of molecular and cellular biology, including:
- How do muscle cells generate force and contract?
- What are the molecular mechanisms underlying cell division and the precise segregation of genetic material into daughter cells?
- How do bacterial toxins hijack host cell machinery to cause infection?
- What is the dynamic landscape of DNA and RNA modifications, and how do they regulate gene expression?
- How is chromatin architecture dynamically remodeled to control access to genetic information?
- What ensures the high fidelity of DNA replication, repair of damage with minimal errors, and accurate segregation of sister chromatids?
- What are the biogenesis, function, and regulation of peroxisomes, key organelles in metabolism and redox homeostasis?
- How do the enzymes in the ubiquitin-proteasome system recognize, modify, and degrade target proteins and can we harness these mechanisms for new therapies?
- Can we design novel chemical tools, such as PROTACs, to achieve targeted protein degradation with precision?
- How is biological information encoded in the diverse architectures of ubiquitin chains, and how are they decoded by the cellular machinery?
- How are epigenetic DNA modifications translated into functional cellular responses?
- What roles do bio-organic radicals play in physiological and pathological processes?
- What is the physiological significance of ADP-ribosylation in signaling, DNA repair, and stress responses?
- How do cells sense and respond to diverse stressors, maintaining protein homeostasis, organelle integrity, and genomic stability?
- Can we engineer synthetic, self-replicating, and evolving biomimetic systems from scratch?
- What universal and cell-type-specific principles govern how cells detect threats and make fate decisions, such as destruction, recycling, or tolerance?
- How can we design programmable nanoscale compartments that mimic essential features of biological systems?
- How is information processing in the brain modulated at the molecular level?
These questions represent the frontiers of modern cell biology. By addressing them with interdisciplinary approaches, spanning biochemistry, structural biology, genomics, synthetic biology, and computational modeling, we aim not only to uncover the fundamental principles of life but also to inspire transformative applications in medicine, biotechnology, and beyond.
APPROACHES
In modern biology, we begin with a compelling biological question and then employ a multidisciplinary arsenal of cutting-edge techniques to answer it. To unravel the molecular mechanisms underlying how biomolecules interact, assemble into functional complexes, become activated, and transmit signals, we leverage a powerful suite of structural and biophysical methods:
- Single-Particle Cryo-Electron Microscopy (Cryo-EM)
- Cryo-Electron Tomography (Cryo-ET)
- X-ray Crystallography
- Nuclear Magnetic Resonance (NMR) Spectroscopy
- Electron Paramagnetic Resonance (EPR) Spectroscopy
- Mass Spectrometry
- Advanced biophysical techniques, including analytical ultracentrifugation, calorimetry, and surface plasmon resonance (SPR)
These approaches enable us to determine high-resolution structures, characterize conformational dynamics, and quantify molecular interactions with atomic precision.
To investigate the spatial organization, mobility, real-time dynamics, and lifetimes of biomolecules within living cells, we combine functional probes with state-of-the-art imaging technologies such as:
- Advanced Light Microscopy: Live-cell imaging, total internal reflection fluorescence (TIRF) microscopy, and light-sheet microscopy,
- Functional Imaging: Förster resonance energy transfer (FRET) and fluorescence lifetime imaging (FLIM),
- Superresolution microscopy: Photoactivated Localization Microscopy (PALM) and stimulated emission depletion (STED) nanoscopy,
- Integrated, multimodal approaches (e.g. single-molecule fluorescence spectroscopy & super-resolution imaging) that combine multiple techniques for comprehensive insights.
As model systems, we use budding yeast and mammalian cell culture models, but we also strongly believe that a powerful path to deep mechanistic understanding lies in reconstitution, building functional biochemical systems in vitro from a minimal set of components. Our goal is to engineer synthetic analogs of complex cellular machinery: from synthetic kinetochores and custom-designed histone complexes with defined modifications, to fully programmable, replicable genetic circuits that mimic the behavior of biomimetic cell-like automata.
Once such synthetic systems are reconstituted, we can ask fundamental questions with unprecedented clarity: What is the minimal set of components required to recapitulate the observed activity? Which molecular interactions are essential for function? How does the system respond to perturbations, environmental changes, or molecular changes?
The insights gained from these minimal, well-defined in vitro systems are then validated and extended in the complex, dynamic environment of living cells or whole organisms, bridging the gap between reductionist experimentation and biological reality.