Our Research Mission

We work to understand the deepest principles of biology by harnessing the power of physics, mathematics, chemistry and computer science. 


Topics

Molecular Theory and Computation

The Dill, Maslov and Wang laboratories use modern statistical mechanics, molecular simulations, and empirical information from the protein database and other experiments to study the protein-folding problem, to map the energy landscapes of folding and molecular recognition, and to understand networks of biomolecular interactions, their evolution and their stabilities in cells. Dill and Wang are developing theory and quantitative study of dynamical processes on the small scale, as in single-molecule experiments and cells. Wang studies biomolecular reaction dynamics in complex environments using path integral formalism to probe the local environments.

The Simmerling, Dill, Rest, Rizzo and Wang labs develop new algorithms for accurate and efficient simulation of large biomolecular systems, for predicting the folded structures of proteins and the binding free energies of ligands to proteins (useful in drug discovery). Rizzo applies Docking and molecular dynamics to identify and optimize drug candidates.

Dill and Simmerling are developing methods for improved conformational sampling. Simmerling, MacCarthy and Wang study molecular recognition. Simmerling and MacCarthy focus on the conformational changes (induced fit) that often take place upon antigen binding to antibodies, to assist in the development and optimization of catalytic antibodies. MacCarthy is also modeling antibody diversity in immunoglobulin genes.

Dill and Simmerling model the properties of water around chemicals and biomolecules, in which specific interactions with solvent molecules are often important. They're incorporating the models into methods of molecular mechanics and dynamics.

Simmerling, Dill, Schatz, and Rest experiment with High Performance and Multi-Core Computing for molecular dynamics, useful for predicting the kinetics and thermodynamic properties of biomolecular systems. Rest develops combinatorial computing environments, algorithms and data structures. Schatz develops scalable algorithms to analyze DNA sequences, to assemble and align next generation sequencing reads, and related analyses. Simmerling and Schatz also create new methods for computer visualization and analysis of molecular structures.

 

Biological Systems and Evolution

Maslov and Wang study the robustness of cellular networks in their noisy fluctuating environments. MacCarthy investigates how robust gene networks evolve to control sex determination. Wang investigates the quantitative dynamics and pathways of cellular networks, and Maslov analyzes how the topological properties of these networks affect their functioning inside living cells.

Rest uses computation, experiments, and natural history to study the evolution of biological systems. He quantitates the changes in cell fitness following changes in gene expression, the fitness costs for expressing certain genes at the same time, and the persistence of variations caused by genetic mutations. He measures the extent that changes in the expression of genes result in changes in the fitness (reproductive capacity) of cells.

Dill and Maslov study how scaling laws and other physics constrain and enable the evolution of cells. Maslov is interested in bio-molecular networks and the underlying changes in genomes in the course of evolution.

Futcher studies the mechanisms that control cell division, the cell cycle, cancer, and ageing. Computer analysis of his experimental results has uncovered a regulatory network involving clusters of genes.

Seeliger wants to understand the molecular mechanisms of signaling proteins and how small molecule ligands and drugs can modulate their activity. He is focusing on two projects: solution dynamics of protein tyrosine kinases involved in cancer, and the substrate spectrum of ubiquitin ligases and conjugating enzymes in aging.

Processes studied by Studier include entry of T7 DNA into its host cell, E. coli; overcoming host restriction; expression of T7 genes and shut-off of host functions; replication, processing and packaging of T7 DNA; and structure and assembly of phage particles.