Physical and Engineering Biology

Faculty from the School of Engineering & Applied Science and the Departments of Molecular Biophysics and Biochemisty (MB&B), Molecular, Cellular, and Developmental Biology (MCDB), and Physics have organized a cross-disciplinary research and education initiative in Physical and Engineering Biology (PEB). With initial funding from the University, we have developed a new Integrated Graduate Program in Physical and Engineering Biology (IGPPEB) that will welcome its first class in the Fall of 2009. IGPPEB will create a new paradigm for graduate and faculty education that transcends traditional, but artificial, boundaries between the physical and biological sciences. IGPPEB will train a new type of scientist, one who excels at applying quantitative reasoning and methods to biological problems, and who possesses the biological sophistication to identify and analyze cutting-edge life-science questions.

Research and teaching in the Physical and Engineering Biology initiative is organized around the eight overlapping and integrated research thrusts (IRTs), which are focused on one of the grand challenges for science in the twenty-first century---understanding how molecular, cellular and ultimately human behavior emerges from the myriad of decision events that occur within biological systems.

Molecular Switches
Understanding the molecular decisions underlying the fate of a nascent polypeptide chain after it emerges from the ribosome is the goal of this thrust area. What determines whether such a protein folds into its functional form, or aggregates and forms amyloid, or is degraded?

Cell Fate
This thrust will investigate how the regulatory mechanisms involved in cell differentiation, cell division, and the coupling between cytokinesis, morphogenesis and the cell cycle emerge from the interplay between the architecture and localization of biological circuits.

Macromolecular Interactions
The vast majority of cellular decisions derive from specific protein-protein interactions. The research of this thrust seeks to describe quantitatively the dynamic network of protein-protein and protein-gene interactions that specify cellular and organismal function via both mathematical models and experimental measurements.

Molecular Motors
Living cells are miniature factories that contain thousands of specialized molecular motors. Helicases, for example, unwind dsDNA and play an essential role in almost every aspect of nucleic acid metabolism, including transcription, replication, translation, DNA recombination and repair, and RNA processing. Elucidating how molecular motors realize deterministic motion out of the thermal chaos of the molecular world is the goal of this thrust.

Gene Expression
All of an organism’s genetic information is specified in the DNA of every cell. What type of cell is made is determined by the particular collection of expressed proteins. The importance of such regulation is becoming ever more appreciated, and chromatin remodeling, which controls the decision of a cell to make or not make particular protein, is the focus of this thrust area.

Sensory Choices
We will investigate experimentally and computationally how an organism decides whether a chemosensory stimulus (odor or taste) is attractive or aversive, while keeping track of the time-dependence of the signal, using the olfactory and gustatory systems of Drosophila and bacterial chemotaxis as models.

Cognitive Decisions
This thrust focuses on decision making in neurons and neural circuits, ranging from the molecular switches underlying synpatic plasticity and learning, to large-scale circuit modeling of stochastic perceptual decision making and reward-based action selection.

Cellular Motion
How is a cell’s response to force and chemical stimulus determined? We will study mechano-transduction in cells in real time, using holographic optical tweezers and speckle microscopy. This will allow us to quantify the interplay of mechanics and biochemistry in neuronal guidance, and to understand how contractile force is coordinated at a subcellular level to power cell migration.

Complete information about the IGPPEB and the interdisciplinary research thrusts of PEB can be found online at https://peb.yale.edu.