School of Humanities and Sciences

Showing 1-10 of 45 Results

  • Chiara Sabatti

    Chiara Sabatti

    Professor of Biomedical Data Science and of Statistics

    Current Research and Scholarly InterestsStatistical models and reasoning are key to our understanding of the genetic basis of human traits. Modern high-throughput technology presents us with new opportunities and challenges. We develop statistical approaches for high dimensional data in the attempt of improving our understanding of the molecular basis of health related traits.

  • Rahul Samant

    Rahul Samant

    Basic Life Science Research Associate, Biology

    Current Research and Scholarly InterestsProtein misfolding in the cell creates toxic species linked to an array of diseases. Protective cellular protein quality control (PQC) mechanisms evolved to selectively recognize misfolded proteins and limit their toxic effects. Molecular chaperones recognize misfolded proteins, while the ubiquitin-proteasome system (UPS) promotes their clearance through the attachment of ubiquitin chains. We previously identified a PQC pathway for spatial sequestration and clearance of misfolded proteins, conserved from yeast to humans, that is amplified when the UPS is impaired. However, the identity of the E3 ubiquitin ligases involved in this pathway—and how they interact with the chaperone machinery—is unresolved. Starting with a fluorescence microscopy-based genetic screen in yeast, we show that distinct chaperone and ubiquitination circuitries cooperate in PQC of soluble misfolded proteins in the cytoplasm and nucleus. In contrast with the canonical model where Lys48-linked ubiquitin chains are sufficient for proteasomal targeting, we found that cytoplasmic misfolded proteins requires tagging with mixed ubiquitin chains that contain both Lys11 and Lys48 linkages to be degraded. Each type of linkage-specific ubiquitination requires a distinct combination of ubiquitin ligases and chaperones. Strikingly, unlike cytoplasmic PQC, proteasomal degradation of nuclear misfolded proteins only requires Lys48 ubiquitin linkages and is independent of Lys11-specific circuits. We conclude that cytoplasmic and nuclear PQC involve combinatorial recognition by defined sets of cooperating systems. The distinct PQC requirements reveal underlying differences in nuclear and cytoplasmic proteome management, with important implications for our understanding of a wide range of diseases.

  • Robert Sapolsky

    Robert Sapolsky

    John A. and Cynthia Fry Gunn Professor and Professor of Neurology and of Neurosurgery

    Current Research and Scholarly InterestsNeuron death, stress, gene therapy

  • Monika Schleier-Smith

    Monika Schleier-Smith

    Associate Professor of Physics

    Current Research and Scholarly InterestsIn between the few­-particle realm where we have mastered quantum mechanics and the macroscopic domain describable by classical physics, there lies a broad swath of territory where quantum effects are relevant but still largely out of our control and partly beyond our comprehension. This territory includes metrological instruments whose precision is limited by the quantum projection noise of millions of atoms; and materials whose bulk properties emerge from many-­body interactions intractable to simulation on classical computers. Professor Schleier­-Smith’s research aims to advance our control and understanding of many­-particle quantum systems by engineering new quantum states and Hamiltonians with ensembles of laser-cooled atoms.

  • Mark J. Schnitzer

    Mark J. Schnitzer

    Professor of Biology and of Applied Physics

    Current Research and Scholarly InterestsThe Schnitzer lab has three major research efforts: 1) In vivo fluorescence imaging and behavioral studies of cerebellar-dependent motor control and motor learning. 2) Development and application of fiber-optic fluorescence microendoscopy imaging techniques for studies of learning and memory in behaving mice and for clinical uses in humans. 3) Development of high-throughput, massively parallel imaging techniques for studying brain function in large numbers of Drosophila concurrently.