Research

My group focuses on several major areas in biology from a systems-wide point of view. Our experiments use a wide range of approaches and employ model organisms as well as mammalian cells. We are also investigating new approaches and technologies that can be applied to unsolved problems in various areas of biology. Some of the current research areas are summarized below. For more details on our current research, see our site at http://openwetware.org/wiki/Silver_Lab.

Synthetic Biology
The ability to logically design biological systems is an exciting new area of research with numerous applications that combines aspects of biology and engineering. Our goal is to both enhance our understanding of the principles of natural biological design, and to develop tools and concepts for designing artificial organisms. In the long term, we hope to develop principles for building novel cells that act as sensors, memory devices, bio-computers, or energy producers, and to build novel subsystems such as proteins with designed properties. Current projects use the advanced operating system afforded by eukaryotes to create artificial proteins with therapeutic value, a cellular oscillator that could lead to pulsatile drug delivery, a cell division counter for analysis of aging, and manipulation/creation of metabolic pathways to produce bio-hydrogen as an economical energy source. These experiments use a combination of theoretical and experimental approaches that are well suited to students with a background in biology, engineering, or any allied field.

 Genome organization
Our studies of nuclear organization concern the spatial and temporal relationships between genes and other nuclear structures and their functional significance. It has become increasingly clear that the organization of genes within the nucleus plays an important role in cell identity and epigenetics. Recent work from our lab has included a genome-wide study of nuclear organization and generating a high-resolution map of gene location. In doing so, we made discoveries concerning the relationship between gene activation and repression. Current interests in the lab include studying the dynamic nature of the genome under different growth states and different cell types, throughout the cell cycle and in response to drugs in development as anti-cancer therapeutics. We also study the dynamics of post-transcriptional regulation and its relationship to the organization of the genome in response to drugs and diseases.

Pathways in Disease
Many signaling pathways employ spatial organization as a key part of their response to environmental stimuli. For example, the movement of key proteins in and out of the nucleus is often one of the downstream steps in signal response. We have taken advantage of this spatial organization to screen for small molecules and genes that affect signaling pathways and therapeutic targets. Currently, we are building on these findings to gain a more quantitative picture of how tumor cells respond to certain drugs. We employ a combination of high-resolution microscopy, genome association technology, modeling and cell-based screens.