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Haussler postdoc Ting Wang wins Helen Hay Whitney fellowship for gene regulation research

Haussler postdoc Ting Wang wins Helen Hay Whitney fellowship for gene regulation research
Haussler postdoc Ting Wang wins Helen Hay Whitney fellowship for gene regulation research
Monday, June 4, 2007

Bioinformatic scientist Ting Wang, who joined biomolecular engineer David Haussler's lab last September for postdoctoral studies, has won the prestigious Helen Hay Whitney fellowship. The fellowship will support Wang for three years of research on regulatory networks for gene transcription.

'Receiving this fellowship shows a recognition for the kind of research I want to conduct and for the environment in which I want to do it,' Wang said. 'Historically, the Whitney foundation has mostly funded, mechanism-driven biomedical research. Funding my research proposal demonstrates that they now appreciate and encourage the younger field of computationally driven regulatory genomics—a new approach that has changed the way modern genomics research is done.'

Wang said that besides the stipend and research money, the symbolic meaning is even more important. "The Whitney foundation aims to train the next generation of leaders in science, which is apparent in their interview process. Getting this fellowship further convinced me that I made a good choice to join the Haussler group at UCSC. This foundation has a history of funding researchers at the top universities in the top groups—the list is a Who's Who of scientists.'

Whitney fellows, their scientific advisors, and a few other selected scientists and Whitney trustees attend a 2-3 day meeting each year to present and discuss their research. 'I believe the annual meeting will offer a pretty decent network of top scientists working on interesting topics,' Wang said. 'I will be able to get to know my peers and their advisors. One of the main things the foundation does for its members is to create a framework for collaboration. Collaboration is the key to success these days.'

'Last year's keynote was a Nobel laureate from Stanford—Andrew Z. Fire. He was a Whitney postdoc. It's cool to know that in your program there are distinguished people like that.'

At UCSC, Wang has gained new perspective on the line of study he began as a graduate student in the computational biology program at Washington University in St. Louis, Missouri. 'I have a different focus now, but the research is interconnected,' he said.

Working in the Wash U genetics laboratory of Gary Stormo, he investigated the regulation of the DNA transcription process. 'This is the most fundamental regulatory mechanism,' he said. 'It touches the basis of a living organism—when and where the genome message is expressed is controlled by this regulation. It is fundamental to understanding life, and it impacts physiology and human diseases.'

'My main interest is one question with two branches,' Wang explained. 'Understanding how genome transcription is regulated will help us understand on a high level what makes a human a human—the difference between species. It will also tell us, on the other end of the spectrum, what makes people different from each other.'

'Researchers can do many things to answer the core questions: What defines a species' and What defines an individual' My angle is transcriptional regulation.' For example, 'human and chimp protein sequences are almost identical. Most people believe that the differences between the species arise from regulatory differences.'

Further, 'individuals within species have differences in protein regulation, and they have a cascade of differences in regulation of their genomes.'

Comparing genomes between individual humans reveals differences in single nucleotides and variations in the number of copies of particular nucleotide segments. These variations come from events that leave the genome with nucleotides substituted, inserted, or deleted. Since most of these variations reside outside of genes, scientists generally agree that these will mostly affect gene regulation.

In graduate school, Wang used data about the origin and evolution of species—phylogenetic data—to identify the binding sites for individual transcription factors. When a transcription factor binds to a binding site, the factor then interacts with general transcription machinery for either activation or repression.

In higher organisms, things can get more complicated. Because proteins interact with each other, combinations—not just one binding site—determine the fate or expression of a gene. So Wang has moved on from simply identifying individual transcription factors to looking for arrays of transcription factor binding sites that can convey identifiable expression patterns. An array of binding sites that interact with each other forms a module—a composition of a variety of signals.

Wang hopes to elucidate the relationship between regulatory modules and the targets they regulate. Discerning these connections will lead to an understanding of the network of cascading interactions that determines the fate of a cell—or an organism.

The emphasis on evolutionary genomics in the Haussler laboratory has expanded Wang's appreciation of how transcription factors work. Exploring how binding sites and modules have evolved aids in understanding their function. Wang said, 'I can construct an evolutionary network to help me study the regulation of that network.'

Understanding the evolution of transcription factors may simultaneously reveal regulatory differences possibly responsible for some human diseases.

Transcript regulation could be fundamental to disease susceptibility, Wang added. 'If mistakes occur at one of the steps, the cell may go to a completely different fate. Some may become cancer. This has direct implications to human diseases.'

'I don't expect to be able to answer this by myself. It will require a lot of scientists to add to the body of knowledge about regulation. I am just trying to tackle the problem from my angle.'

Wang has a related project that continues a line of research he started before graduate school, when he was a medical research technician in the Rainer Brachmann laboratory at Wash U. This continuing work is a part of the ENCODE project, an NIH project aimed at discovering all of the functional elements in the human genome.

Brachmann, now at UC Irvine, developed a screening strategy for transcription factor binding sites, a technology using yeast to screen for genomic fragments that can be activated by transcription factors. He plans to look for all of the transcription factors in the human genome.

While working in the Brachmann laboratory, Wang earned a master's degree in computer science on the side, because thought it would launch his biology career in a different direction. He didn't know that one day he would be doing computational biology until he was half way through the master's degree, 'That's when the genome project blossomed, and I found myself very well equipped to go after that path,' he said.

Before coming to the US, Wang was a biology student at Peking University in Beijing, China. As a student, he worked part-time as a television news anchor for two different programs: one aimed at relating the essence of Chinese culture to the world, and the other taking advantage of the new wave of privately owned cars to introduce ideas about where people could go in their leisure time.

At UCSC, he loves working in the Haussler lab, 'it's comfortable, has great resources and colleagues, and the setting is beautiful.' On the science side, he went on to say, 'Before I came here, I used to look at the data form the transcription side. Now that I'm here, I am looking at the evolution side, too. This allows me to see things differently.'

The Whitney Foundation supports early postdoctoral research training in all basic biomedical sciences. To attain its ultimate goal of increasing the number of imaginative, well-trained, and dedicated medical scientists, the foundation grants financial support of sufficient duration to help further the careers of young scientists engaged in biological or medical research. The foundation awards 20 three-year research fellowships annually—more than 900 since its inception.

Five current UCSC faculty members are former Whitney fellows: Thomas Schleich (1968), Bill Sullivan (1985), Doug Kellogg (1991), Theodore Holman (1991) and Melissa Jurica (2000).