Chicago Science: Genomic Researchers Target Cancer, Diabetes, GI Disease

The Human Genome Project has greatly accelerated the pace of genetic discovery and made it realistic to envision a day when medical care will be tailored to each person's unique DNA sequence.

But before genetically personalized medicine can become a reality, scientists must find ways to master the overwhelming breadth of this "book of life" and the complexity of the biological systems it encodes.

Many single genes have been discovered that, acting alone, cause particular defects and illnesses. Now scientists must identify the vast networks of genes at work in common devastating diseases, such as cancer and diabetes. How do genes interact with one another and the environment to influence an individual's state of health? How can researchers use that knowledge to invent new cures, determine the optimal treatment for each person, and predict individual risk in order to prevent disease altogether?

DECIPHERING DNA'S HIDDEN MESSAGE

The Institute for Genomics and Systems Biology (IGSB), launched last year in collaboration with Argonne National Laboratory, is Chicago's intellectual home for the study of gene networks. It links evolutionary biologists, genetic theorists, genomic experimentalists, mathematicians, computer scientists, clinicians, ethicists, and economists. Under the leadership of geneticist Kevin White, PhD, a pioneer in genomics and systems biology, the IGSB's list of fellows has grown to include more than seventy Chicago faculty members and Argonne scientists.

Like any code-breakers, scientists seeking to solve the genomic cipher face a formidable barrier in what's known as the "curse of dimensionality." It stems from the sheer size of the genome, which is composed of three billion chemical "letters" comprising some 25,000 genes. Looking at all possible two-gene or three-gene combinations within the genome would entail searching combinations numbering in the billions and trillions, respectively. Some diseases are almost certainly caused by dozens or even hundreds of genes.

CLUES FROM EVOLUTION

Even with today's supercomputers and automated screening laboratories, possible gene combinations are so vast that researchers could never test them all. At the IGSB, evolutionary biology and genetic theory are providing clues to narrow the search.

In 2006, for example, White led a group of researchers who compared more than a thousand selected genes from humans, chimps, orangutans and rhesus monkeys. They discovered that transcription-factor genes, genes that regulate other genes by turning them on or off, evolved much faster than other kinds of genes in humans. This finding helps account for what

The study also found that slow-evolving genes are associated with specific human diseases when they are inappropriately regulated by the transcription-factor genes. This finding shows that the evolution of gene regulation cannot be ignored in the search for genetic causes of disease in modern populations.

To tie gene patterns to specific diseases, the IGSB's experimentalists turn to tissue samples provided by patients and stored in the Medical Center's extensive biobanking operation. Using new methods of rapid, automated genetic screening, they will look for commonalities among the gene profiles and molecular states (levels of proteins produced by those genes) of these samples and compare them with the conditions of the donors indicated by their patient records. This linking of genotype and phenotype will reveal the underlying genetic "architecture" of cancer and other common diseases. White's team at Argonne has developed one of the world's highest-capacity genome-scanning facilities: the High Throughput Genome Analysis Core, which can scan expression profiles for nearly a thousand human genomes per week.

FROM GENES TO GENOMIC MEDICINE

Chicago's researchers are approaching the genomic puzzle from another angle, using a mode of scientific inquiry that didn't exist a few decades ago. By creating detailed computer simulations of the complex gene-protein interactions suspected to underlie disease, they can study molecular activity too small to be observed directly. Researchers tweak these electronic models, adding or subtracting "virtual" molecules, to see if such changes produce molecular states characteristic of disease.

The final, most formidable challenge is translating all this information into clinical treatments. Despite the explosion of knowledge and the extensive media attention given to "personalized medicine," only a handful of genomic breakthroughs have made the leap from lab to bedside to provide new tests or medicines.

Within the interdisciplinary framework of the IGSB, scientists will seek new drug treatments, use nanotechnology to devise new methods of diagnosis and drug delivery, and develop genetic tests that will enable physicians to tailor drug treatments to individuals.

In this initiative, research will focus first on cancer, diabetes, and inflammatory bowel disease, three areas for which the Medical Center's patient care is ranked among the best in the nation. With success against any one of these diseases, we will have developed the prototype for a new model of interdisciplinary research.

The IGSB's vision extends beyond new tests and treatments. With a nationally recognized program in medical ethics, we expect to be a strong voice in the national discourse on the many ethical questions that arise with increased availability of genomic information about individuals.

AN INVESTMENT THAT WILL CHANGE THE FACE OF MEDICINE

Chicago will invest more than $200 million in this initiative over the coming decade. With significant help from donors, the University will:

• Recruit 10 to 15 additional faculty, with the immediate focus on database design, medicinal chemistry, clinical genomics, stem cells, cancer informatics and metabolic genomics.
• Create endowed faculty positions and help new investigators establish programs.
• Build or renovate space for new and current researchers.
• Launch new programs in basic science and translational research.
• Build and staff shared research facilities to provide state-of-the-art equipment and expertise.
• Develop a bioinformatics system to link the Medical Center's biobanking facilities to both patient histories and genomic data derived from cellular screening.

In the quest to establish a new era of medicine, the University's tradition of philanthropic support will be as important as its traditions of scientific discovery and unsurpassed patient care. All of these factors are keys to deciphering the genomic enigma.

Read more about how to make a contribution to the Spark Discovery, Illuminate Life campaign and to make a gift online.