Energy and synergy

Himadri B. Pakrasi, Ph.D., has an impressive title, one that speaks volumes about who he is, what he has done and what he is doing. Pakrasi, the George William and Irene Koechig Freiberg Professor of Biology in Arts & Sciences, and professor of energy in the School of Engineering, has a title that transcends what have been boundaries at Washington University.

His titles bridge two schools that have had minimal interaction, but in recent years have found, thanks to Pakrasi, common themes: energy, the environment and sustainability. These are the themes Pakrasi, a native of Calcutta, India, has pushed in his own research since he came to the United States in the late 1970s to pursue a doctoral degree.

An example: In recent years Pakrasi, using humble photosynthetic bacterium, has assembled multidisciplinary teams of researchers to unravel the mechanisms of how organisms harness available energy. He has received funds from two federal agencies in the quest, and has changed the way biology is done by harnessing the skills and insights of researchers from across the University and the world.

On June 4 of this year, Chancellor Mark S. Wrighton announced that the University is creating a new International Center for Advanced Renewable Energy and Sustainability (I-CARES) to encourage and coordinate University-wide and external collaborative research in the areas of renewable energy and sustainability — including biofuels, CO2 mitigation and coal-related issues. The University will invest more than $55 million in the initiative.

In recognition of Pakrasi’s expertise in these areas and of his coalition-building skills, Wrighton named Pakrasi the director of I-CARES, located in the newly refurbished Wilson Hall.

“I-CARES is a new experiment for this University, and it’s the kind of bold thing that an institution like ours can attempt,” Pakrasi says. “I-CARES shows that it’s time for us to integrate things that are happening all over the University. All of the schools are showing interest. There never has been this kind of synergy before, and we owe it to our chancellor’s initiative, commitment and vision.”

Another program the chancellor envisioned and enacted — and of which Pakrasi plays a part — is an international partnership of leading universities in Asia, the Middle East, Europe and Latin America. The partnership was forged recently by the University’s McDonnell International Scholars Academy. I-CARES and the McDonnell Academy will collaborate, giving I-CARES an international flair.

Pakrasi’s first loves were physics and mathematics. In the early 1970s, he received undergraduate and graduate training in physics at the prestigious Presidency College and University of Calcutta and began a physics doctoral program there. That’s also about the time he became interested in biology, specifically the phenomenon of photosynthesis. But changing courses in India was not encouraged, Pakrasi says, and to this day he is recognized as a physicist, not a biologist, in his native country.

He came to the United States in 1978 to switch to natural science and to enter a program in biology, first at the University of Rochester, where he earned a master’s degree in biophysics in 1980, then the University of Missouri-Columbia.

At Missouri, Pakrasi met his wife, Maitrayee Bhattacharyya, who at the time was a doctoral candidate in biochemistry. She was also a Washington University alum, having obtained a bachelor’s degree in biology. They married in 1982, and have a daughter, Annapurna, 10. Now Maitrayee, who has a doctorate from the University of Notre Dame, works with Pakrasi as a research associate in his lab.

Following the completion of his doctorate in biology at Missouri in 1984, Pakrasi went to Michigan State on a postdoctoral fellowship to continue studying photosynthesis. He was a visiting scientist at DuPont in the mid-’80s when he began research on Synechocystis 6803, a cyanobacterium, microscopic blue-green unicellular algae that captures sunlight and then carries out a variety of intriguing biochemical processes. Cyanobacterial species continue to be the backbone of Pakrasi’s research.

Pakrasi favors working in academia, but he credits industry for incubating some of his most pivotal insights. “People have the notion that in industry you have to do specific product-related research,” Pakrasi says. “But this wasn’t the case for me then. Scientists there were just beginning to learn about cyanobacteria, and I was on the ground floor of some discoveries about key genes and proteins. They wanted a model organism that could provide lots of insights into what goes on in plants. Cyanobacteria are progenitors of plants that shed light on the functions of plant chloroplasts.

“DuPont gave me the opportunity to get into a completely new area of science where not much was known. They very kindly allowed me to bring the basic knowledge that I learned there to Washington University when I started my lab in 1987.”

This beautiful friendship between Pakrasi and cyanobacteria culminated in 2006 when the U.S. Department of Energy (DOE) devoted $1.6 million to sequencing the DNA of six photosynthetic bacteria. University biologists began examining the bacteria for their potential as one of the next great sources of biofuel.

Pakrasi and his collaborators designed a photobioreactor to watch Cyanobacteria convert available sunlight into thick mats of green biomass, from which biofuel can be extracted. Pakrasi also led the sequencing of Cyanothece 51142 at the Washington University Genome Sequencing Center as the focus of a DOE “grand challenge project.” This information may yield clues to how environmental conditions influence key carbon fixation processes at the gene-mRNA-protein levels in an organism.

The sequencing is an integral part of one of the most critical environmental and energy science challenges of the 21st century being addressed as part of a grand challenge project at the W.R. Wiley Environmental Molecular Sciences Laboratory, a national facility managed by the Pacific Northwest National Laboratory for the DOE. This program features an elaborate international collaboration involving 10 national laboratory groups and six university laboratories, including Washington University.

And who was selected to be leader of the grand challenge project? Pakrasi. It marked the first time that the DOE had chosen a university scientist to lead such an endeavor in a national laboratory.

Pakrasi points to a sabbatical he took in 2002 at the former Pharmacia — now Pfizer — as being crucial in landing the DOE grant and one other National Science Foundation (NSF) grant. He found himself at a point in his career where all of the quantitative training he had received in physics, math and statistics was becoming more relevant in biology. At Pharmacia, scientists were using a novel method of gathering and analyzing data that is now called systems biology.

Systems biology is the study of complex networks of interactions occurring between and within living organisms. A primary focus of systems biology research at the cellular and molecular level is to examine how a change in conditions — such as a change in environment, introduction of a mutation or exposure to a drug — affects the expression of every gene in a particular cell and to understand what genetic or biochemical interactions stimulate these changes.

Because of the large data sets, advanced computational methods, sophisticated technology and complex biological questions involved, systems biology is dependent upon collaborative, interdisciplinary efforts between groups of researchers with expertise in mathematics, computer science, physics, engineering, statistics, chemistry and biology.

“I observed their large-scale, extensive networks of different researchers, their approach to analyzing data. Even before I came back to Washington University I was ready to change our approach,” Pakrasi says.

He began organizing two large-scale system biology projects, a NSF study in redox biology and the DOE’s project. In these projects he uses a systems approach to understand the network of genes and proteins that governs the structure and function of membranes and their components responsible for photosynthesis and nitrogen fixation in two species of unicellular cyanobacteria, specifically Cyanothece and Synechocystis.

Pakrasi’s many efforts are not lost on Ralph S. Quatrano, Ph.D., the Spencer T. Olin Professor and chair of the Department of Biology in Arts & Sciences. “Our vision in this century is to integrate biology with the physical and engineering sciences,” Quatrano says. “This cross-disciplinary effort will take leaders who have made and understand this transition and the potential that integration holds for each discipline.

“Himadri is such a person, having received his Ph.D. in physics and having made significant contributions to our understanding of the basic process that combines photochemistry with biology, that is, photosynthesis,” Quatrano said. “He is unique in that he has the recognition by the scientific community for his research contributions, a strong background in the physical sciences and a vision for how these disciplines can by harnessed to approach the complex questions facing our planet — energy and sustainability the prime ones. Himadri is the ideal person to lead this initiative.”

Harnessing all the knowledge he gained from past experiences, Pakrasi is ready to direct the unique brain trust known as I-CARES. “I think of the ‘C’ in I-CARES as ‘catalyst,'” Pakrasi says. “If we can bring someone from law and architecture to the same table as people from medicine and Arts & Sciences, then we have the forum to come up with novel ways of making energy and making the environment renewable and sustainable.

“I will consider I-CARES a success if we can bring seemingly disparate people together where we talk, learn and collaborate with each other.”