Research

Our biochemistry faculty is pursuing a broad spectrum of research interests, including:

  • Structural biology
  • Molecular neuroscience
  • Developmental biology
  • Systems biology
  • Virology
  • RNA biology
  • Single molecule biophysics and single cell genomics

Major Research Areas

Structural Biology

Several members of the Department are leaders in solving macromolecular structures of biomolecules and their complexes using X-ray crystallography, NMR spectroscopy, and Cryo Electron Microscopy. These studies are complemented by active programs in macromolecular function and structural analysis, including research in macromolecular dynamics, computational biology, electrostatics, and bioinformatics.

Anthony Fitzpatrick studies the structures of protein aggregates implicated in neurodegenerative diseases using CryoEM. For example, the structure of Tau protein filaments in Alzheimer’s disease.

Joachim Frank investigates the mechanism of protein synthesis on the ribosome using cryo-EM and single-particle reconstruction, leading to an understanding of the dynamics of the decoding and translocation mechanisms involved in mRNA translation. He also develops methods for time-resolved cryo-EM to study short-lived states (20 to 1000 ms) in biomolecular reactions, and methods for mapping the energy landscapes of biomolecules from single-particle cryo-EM datasets..

Wayne Hendrickson uses both X-ray diffraction and CryoEM methods to solve structures of membrane proteins and macromolecular protein complexes.

Barry Honig develops computational approaches for calculating macromolecular electrostatics and its thermodynamic influence on folding and intermolecular interactions. Bioinformatics research includes structure-based sequence analysis, threading, homology model building and databases of protein-protein and protein-ligand interactions.

Arthur Palmer develops new methods in NMR spectroscopy and the applies these methods to study structure and dynamics of macromolecules, particularly the contributions of conformational dynamics to folding, molecular recognition, and catalysis.

Lawrence Shapiro uses structural information obtained from X-ray crystallography to direct biochemical studies of biological problems, particularly involving neuronal cell adhesion, cell-cell interactions, and neural patterning.

Alexander Sobolevsky studies structure and function of ion channels using biochemical and biophysical methods, including cryo-EM, X-ray crystallography, electrophysiology and fluorescence measurements.

Anna-Lena Steckelberg uses x-ray crystallography and cryoEM to study structure-function relationships of viral RNA and RNA-protein complexes.

Molecular Neuroscience

Columbia University is a leading center for studies in Neuroscience, and several faculty members have joint appointments in the Department of Neuroscience.

Richard Axel pioneered studies of the molecular basis of odorant perception and is currently interested in the relationship between innate and learned responses to sensory input.

Oliver Hobert studies the molecular basis of neural circuit assembly, gene regulation and behavior in C. elegans.

Eric Kandel combines behavioral, cellular, and molecular biological approaches to delineate the changes that underlie simple forms of learning and memory in invertebrates and vertebrates, and has a recently focused on aging and cognition.

Arthur Karlin studies the mechanisms for signal recognition, gating, conductance and selectivity in neurotransmitter receptors.

Stavros Lomvardas studies the cellular and molecular mechanisms that generate neural diversity. He uses the olfactory system to study the mechanisms of the stochastic and monoallelic expression of olfactory receptor genes in mice.

Tom Maniatis studies the role of cell surface diversity on neural circuit assembly in mice through studies of the genomic organization, expression, and function of clustered protocadherin proteins. He also studies the molecular mechanisms of neurodegeneration through studies of ALS using human and mouse stem cells, mouse models.

Richard Mann studies how the neural circuitry that is required for coordinated walking in adult flies is constructed during development, and how it functions in the adult.

Alexander Sobolevsky studies structure and function of ionotropic glutamate receptors (iGluRs), which mediate the majority of excitatory neurotransmission in the central nervous system, using cryo-EM, X-ray crystallography, electrophysiology and kinetic modeling.

Charles Zuker studies taste perception in both Drosophila and mice, and combines molecular, genetic, and physiological approaches to investigate the biology of sensory transduction.

Developmental Biology

Iva Greenwald uses the nematode, Caenorhabditis elegans, to study how cells communicate with each other to specify fate determination during development.

Oliver Hobert studies the role of transcriptional regulatory elements in the establishment of neuronal cell identity and circuit development in C. elegans.

Richard Mann studies how homeodomain-containing transcription factors control developmental pathways, and how motor neurons are specified in Drosophila melanogaster.

Systems Biology

Andrea Califano uses a combination of computational and experimental methodologies to study the regulatory logic of human cells in genome-wide fashion. His findings have been translated into studies in which disease master regulators are identified and pharmacologically targeted on an individual patient basis.

Barry Honig integrates different types of data, to develop holistic models that more comprehensively describe networks of protein-protein interactions that give rise to biological function.

Laura Landweber investigates RNA-mediated epigenetics and genome reorganization during development and evolution.

Peter Sims takes a systems-level approach to understanding cellular behavior by collecting large-scale genomic data and using computational methods to gain biological insights. He has developed and applied novel single-cell sequencing methods to understanding mechanisms of oncogenesis.

Saeed Tavazoie focuses on understanding cellular adaptation, in particular how cells achieve adaptive gene-expression states. He takes a systems-level approach to understanding cellular behavior by making large-scale global observations and using computational approaches to infer the key underlying components and their organization into regulatory and genetic networks.

Chaolin Zhang uses a combination of computational and experimental methods to infer RNA regulatory networks in the nervous system. In particular, he is interested in characterizing the regulatory networks that specify neuronal cell types, and how these networks can be compromised in certain pathologic contexts, such as brain tumors and neurodegenerative diseases.

Virology

Steve Goff studies the genetics, replication, and life cycle of the Moloney murine leukemia virus (M-MuLV) and the human immunodeficiency virus type 1 (HIV-1).

Max Gottesman studies the regulation of transcription termination in E. coli and its bacteriophage and is particularly interested in how transcription termination is coupled to translation, DNA replication, and chromosome integrity.

Anna-Lena Steckelberg studies how RNA viruses of the coronaviridae, flaviviridae and tombusviridae families manipulate the RNA metabolism of infected cells.

RNA Biology

Laura Landweber investigates RNA-mediated epigenetics and genome reorganization during development and evolution.

Tom Maniatis studies the mechanisms involved in generating mature protocadherin mRNAs through a combination of stochastic promoter choice and RNA splicing. In addition he studies the role of anti-sense non-coding RNAs in promoter choice.

Sam Sternberg studies the molecular mechanisms of adaptive immunity in CRISPR–Cas systems using biochemical, structural, and biophysical approaches. He also uses RNA-guided DNA targeting enzymes to develop novel genome engineering tools.

Anna-Lena Steckelberg studies the role of RNA turnover and RNA quality control pathways during infection with RNA viruses, and how viruses use RNA structure to manipulate cellular processes.

Chaolin Zhang uses a combination of computational and experimental methods to infer RNA regulatory networks in the nervous system. In particular, he is interested in characterizing the regulatory networks that specify neuronal cell types, and how these networks can be compromised in certain pathologic contexts, such as brain tumors and neurodegenerative diseases.

Single Molecule Biophysics and Single Cell Genomics

Eric Greene studies dynamic protein DNA interactions using single-molecule optical microscopy to study fundamental interactions between proteins and nucleic acids. His goal is to reveal the molecular mechanisms for DNA repair, recombination, and transcription.

Tom Jessell studies cellular diversity in the spinal cord, focusing on the expression of specific genes in individual cells to define specific neuronal cell types.

Tom Maniatis develops single-cell sequencing methods to study the dynamics of cellular differentiation of ES and iPS cells to motor neurons. His laboratory also collaborates with Richard Axel’s lab to combine single cell transcriptomics, optogenetics, and behavioral assays to better understand cell-type-specific contributions to mammalian behavior.

Peter Sims develops single-cell sequencing methods and applies them to the study of cellular heterogeneity in cancers during disease progression.