BIO5 | Genome Structure and Function Consortium

Research Initiatives

Genome Structure and Function Consortium (GSFC)

The new technologies of genomics, proteomics, metabolomics and bioinformatics have begun to generate knowledge that will revolutionize healthcare and agriculture. Deciphering genomes and determining the functions of tens of thousands of genes are tasks that scientists can only tackle by joining forces in multidisciplinary and often multinational teams. The results are fed into large public databases on genome sequences, gene expression patterns (at the RNA and protein levels), and metabolism. The shared databases provide a foundation that makes the broad field of genomics a highly unified endeavor, despite its interdisciplinary nature. BIO5 is building on strong, nationally and internationally recognized UA research programs in genomics (especially plant and microbial genomics), evolutionary biology, biochemistry and molecular biology, to focus on the six subareas detailed below.

Faculty participating in the Genome Structure and Function Consortium

Genomics Research Network

BIO5 researchers are advancing experimental genomics science and technology to investigate the intricate networks of genes in humans, animals, plants and microbes. They are developing and testing new methods to obtain and analyze genomic data. They analyze gene expression in cells, tissues and organisms, using high throughput methods such as microarrays, fluorescent proteins, confocal microscopy and bioinformatics. Proteins are analyzed using state-of-the art proteomics and structural biology methods. The human medical genetics component is working to discover possible genetic bases of cancer and respiratory diseases.

Functional Genomics Facilities

Interfering with a gene's function and analyzing the consequences reveals clues about that gene's role in the interplay of gene and protein networks. Because all living organisms share common ancestry, their genes and basic cellular processes show extensive similarities, even between such different organisms as plants and humans. Thus findings from one species can be extended to many others. This allows for the use of a few model genetic systems to gain understanding of a large number of biological processes in diverse species. Using well-studied model organisms for gene function analyses, researchers can better understand what causes a disease, discover and test new drug candidates and translate novel therapeutic strategies to medical practice. The Mammalian Functional Genomics Facility will provide genetically modified mouse lines for basic and translational investigations. The Invertebrate Functional Genomics Facility will provide genetically modified Drosophila (fruit fly) and yeast lines for investigating basic mechanisms of gene function. Since many aspects of cellular biology are shared among organisms, many studies can be performed faster and less expensively using invertebrate model organisms. Once results are obtained in the invertebrate systems, the mouse facility will be used to demonstrate similar findings in a mammalian system prior to moving on to human clinical trials.

Genetic Improvement of Plants

Global population is expected to peak at 10 billion in the next 50 years. Since the best agricultural land is already under cultivation, producing more food with proper stewardship of the world’s remaining natural ecosystems will require increasing the productivity of the land. As global warming and soil salinization continue, researchers need to understand how genes in plants and animals influence their sensitivity to drought and salty soil. Using comparative and functional genomics, proteomics and metabolomics, BIO5 scientists investigate gene control to improve crop plants. Target improvements include nutritional quality and resistance to stress, pathogens and pests. Engineering crop plants also holds great promise for the medical field, through investigating plant compounds as potential new drugs and using plants to produce pharmaceuticals.

Respiratory Immunobiology Program

Complex lung diseases, e.g. asthma and chronic obstructive pulmonary disease (COPD), have a major impact on people’s health and life in the United States and Arizona. An intricate interplay between genetic and environmental factors leads to chronic lung inflammation and severe breathing problems. Through an approach that integrates epidemiology, genomics, immunology and respiratory biology, the Respiratory Immunobiology Program seeks a mechanistic understanding of these diseases so as to devise new, effective treatments. Asthma affects 12-15 million Americans and is reaching epidemic levels in children. COPD, which is strongly linked to smoking, affects more than 15 million adults and is the fifth leading cause of death in the country. In Arizona, according to the American Lung Association, there are over 250,000 COPD patients and almost half a million asthmatics, one third of whom are children. The genetic mechanisms and environmental contexts that predispose to complex lung diseases differ among individuals. Therefore, devising effective therapies and ultimately curing these diseases requires a “personalized medicine” approach. A combined effort between BIO5 and the Arizona Respiratory Center, integrating genetics, immunology, respiratory biology and medicine, is needed.

Epigenetics Program

It is becoming increasingly clear that the mechanisms governing how genetic information is transmitted and interpreted do not rely solely on the information encoded in the genes. Other factors, too, play a role in determining a gene's state of activity, for example certain proteins that are associated with DNA. For the most part, cells do not store their genetic information as naked DNA molecules but in a tightly packed and highly ordered structure referred to as chromatin. Chromatin consists of the thread-like DNA molecule wrapped around specialized "packing" proteins and several other proteins associated with DNA. These proteins play a major role in epigenetic gene regulation, as they can be modified in certain ways that influence chromatin structure. For example, the packing proteins can undergo changes in their three-dimensional structure and thereby either loosen or tighten their grip on the DNA, making its information content more or less accessible. Such epigenetic phenomena are associated with certain cancers, neurological diseases, diabetes, responses to environmental toxicants and influence the efficacy of gene therapies.

BIO5 is developing a world-class epigenetics program by building on a solid base of basic researchers working with model systems to investigate underlying mechanisms and expanding partnerships with scientists working on specific diseases or agricultural applications.

Biotechnology Core Facilities

Partnering with the Arizona Research Laboratories Biotechnology Division, BIO5 enables researchers across the university, as well as collaborators, access to cutting edge technologies in genomics, proteomics and bioinformatics. The Genomics Core Facility provides DNA sequencing, custom microarrays, fragment analysis, SNP detection, sample purification and real time PCR. The Proteomics Laboratory provides one- and two- dimensional electrophoresis coupled with mass spectroscopy for protein identification, purification and quantification and provides circular dichroism, calorimetry and FT-IR for protein characterization. The Biotechnology Computing Facility provides leading edge solutions for data acquisition, data management, distribution and analysis.