From the tiny to the tinier, studying life’s big secrets

Scientists in two new research centers at West Campus — the Systems Biology Institute and the Microbial Diversity Institute — are taking different approaches to understanding the processes that govern life on earth.

Here is a brief look at their work.

Systems Biology Institute: Putting Humpty Dumpty together again

New technology has given scientists the ability to identify, track and visualize minute molecular processes, and has created a tidal wave of biological data. Now those researchers are seeking innovative ways to put the information to good use.

The need to organize, analyze and ultimately derive meaning from this treasure trove of information was the driving force behind the creation of the Systems Biology Institute. There scientists from a host of disciplines such as physics, computer science, math, engineering and biology will collaborate to decipher how life orchestrates thousands upon thousands of molecular events at lightning speed and enables organisms to survive.

“The trend in 20th-century biology was to take things apart and find the smallest building blocks of life,” says Gunter Wagner, the Alison Richard Professor of Ecology and Evolutionary Biology and chair of the institute’s advisory committee. “We did a pretty good job at that and now have technologies that can help us see how they work together. For the first time we have a realistic chance to put Humpty Dumpty back together again and find out how organisms work.”

The new institute boasts three of what Wagner hopes will eventually be nine labs operating at West Campus. Friday, Oct. 15, marks a milestone of sorts when the institute hosts an international cast of speakers at the Yale Systems Biology Institute Symposium. The event features speakers who will address a host of topics such as synthetic biology, genetic regulatory networks, and creation of computer models of biological activity.

(The event runs from 8:30 a.m. to 6:30 p.m. at Building WB-25 and is open to the Yale community.)

The breadth of the topics at the symposium mirrors Wagner’s vision for the Systems Biology Institute. The institute will focus on three broad and ambitious missions: creating modeling systems that will use biological data to predict the behavior of living cells; developing new technologies to help researchers analyze biological activity in real time; and using principles of evolution to understand biological function.

In one institute lab, Jesse Rinehart, assistant professor of molecular physiology, is devising a way to adopt mass spectronomy to measure phosphorylation of proteins, a critical life process by which proteins change shape and function. In a soon-to-be-opened second lab, Farren Isaacs, assistant professor of molecular, cellular and developmental biology, has devised a way to create quickly hundreds of planned genetic mutations. The technology will allow scientists to determine functions of many different genes in complex regulatory networks that govern much of life.

Changes in those networks drove evolutionary change and are of particular interest to Wagner, who is investigating the origin of pregnancy in mammals.

Wagner says that understanding evolutionary change can help decode the bewildering complexity of these regulatory networks.

An apt analogy, Wagner explains, is the fact that “no one began to understand the function of the human brain until they compared its structure to those in other animals.” In the same way, Wagner today uses comparative analysis of reproductive systems of mammals and those of reptiles and fish to tease out the genetic basis for the rise of mammalian pregnancies.

Microbial Diversity Institute: Tracking the big impact of world’s tiniest organisms

Bacteria and viruses influence all aspects of life on earth, so scientists at the new Microbial Diversity Institute are studying the impact of these tiny organisms on everything from human health to insect behavior to biological and physical environments, says Howard Ochman, director of the institute and professor of ecology & evolutionary biology.

“This will be one of the best places at Yale to do creative research,” asserts Ochman, who was recruited earlier this year from the University of Arizona to launch research integrated research programs at the West Haven campus.

Ochman wants to cultivate the same varied, yet thematically linked, research efforts at the Microbial Diversity Institute. Within a year, he expects to have four faculty members operating labs at West Campus, a number he hopes will at least double in the coming years.

Newly hired Andy Goodman, for instance, will study genomes of symbiotic bacteria living in the digestive tracts of mammals when he arrives in January. His research will allow scientists to understand the impact of individual bacterial genes on human health.

Another new researcher, Eduardo Groisman, studies how pathogenic microbes sense signals from the environment and flourish in the host environment. One goal of his lab is to control the virulence of pathogens in hosts.

Nancy Moran is known for studying the often-strange symbiotic relationships between bacteria and various plant-feeding insects. One of her research projects will be to study interactions of bees and microbes, work that has implications for agricultural production.

Ochman’s own research focuses on the evolution and dynamics of bacterial genomes, and how they gain and lose genes. Other projects in his lab survey the microbial world within non-human primates.

According to Ochman, all these efforts will be greatly enhanced by the proximity to the Systems Biology Institute at West Campus, which focuses on complex interactions in biological systems and the regulatory networks that govern life.

“There is nothing else like this anywhere,” Ochman said. “We are going to try to tie all this together and get people talking to each other, all on the same floor.”

Ochman also plans to bring national experts to West Campus in a series of symposia. The first was held Oct. 1 and featured Bonnie Bassler of Princeton University, who discussed how communities of bacteria communicate with each other, an ability that affects their pathogenesis and virulence. In addition, Ed DeLong of the Massachusetts Institute of Technology talked about interactions among marine microbes, the most abundant organisms on Earth, and Eddie Holmes of Penn State University discussed the evolution and origins of influenza viruses.

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