University of Florida Genetics Institute Strategic Plan – 2005
The discovery of the three-dimensional double helix architecture of DNA in 1953 was not only a defining moment for biology but arguably one of the most significant scientific achievements of all time. It fundamentally and permanently changed the course of biology and genetics.
The unraveling of DNA’s structure, combined with its elegant mechanism for self-replication and the existence of a universal genetic code for all living beings, have together provided the basis for the understanding of fundamental cellular processes, mutation and genetic repair, genetic variation, the origin of life and evolution of species, and the structure/function/regulation of genes. The double helix is also proving to be of immense significance to advances in agriculture, medicine and such other diverse fields as anthropology, criminology, computer science, engineering, immunology, nanotechnology, etc.
It was the study of DNA that led to the development of tools that brought about the biotechnology revolution, the cloning of genes, and the sequencing of entire genomes. Yet most knowledgeable people agree that what has been achieved in DNA science thus far is only the beginning. Bigger and better applications, which will impact directly on the quality of human life and sustainability of life on earth, are yet to come.
In order to attain these objectives, the digital nature of DNA and its complementarity are beginning to be exploited for the development of biology as an information-based science. Indeed, a paradigm shift is already taking place in our view of biology, in which the natural, physical, engineering and environmental sciences are becoming unified into a grand alliance for systems biology. Indeed biology in the 21st century will be surely dominated by this expanded vision.
During the past two decades the University of Florida has made substantial investments in human resources and infrastructure to support teaching and research in basic as well as applied genetics (biotechnology). Unfortunately, genetics faculty and programs are scattered all around the campus in various departments and colleges, with little linkage and much duplication. The Genetics Institute mitigates these problems by offering a cohesive and unified systems biology program for the entire campus, devoted to excellence in teaching and research that will foster inter-disciplinary interactions and collaborations.
Research Priorities in Genetics
The sequencing of the human genome, and those of several microbial and plant species, has generated enormous amounts of raw data that cannot be of much use without further comprehensive analysis, and without establishing relationships between genes and their functions. With the advent of high-throughput sequencing methods and equipment, the generation of extensive molecular datasets has become relatively straightforward and feasible even for small, single-investigator laboratories.
However, analysis of these data has become increasingly complex and the development of new analytical methods has not kept pace with the generation of molecular data. Functional analysis, i.e. determination of the effect of particular genes and genetic variants and correlation with specific phenotypes, will require the development of novel analytical tools and additional sequence data from key specimens and organisms. Furthermore, the study of heritable modification of DNA, i.e. epigenetics, is emerging as a critical new field as we discover that the DNA sequence is not the final word in genetics.
The University of Florida Genetics Institute (UFGI) is well positioned to play a lead role in the post-sequencing era. We have identified four key areas in which to target future hires in order to build on existing strengths and improve our position in genetics nationally and internationally. Our strategy is to focus on (1) the generation of primary data in the form of additional DNA sequences in areas of specific relevance to UF and epigenetic data with clinical application, and (2) the development of novel analytical tools applicable across all organisms and genomes. The four research areas are listed below with brief definitions and are further developed in the following sections.
- Bioinformatics – the analysis of sequence/structure/expression data
- Comparative genomics – the comparison of genomes, genes, and gene functions across organisms
- Population and statistical genetics – computational and statistical methods for analyzing and interpreting genetic data
- Epigenetics – the analysis of mechanisms governing heritable patterns of differential gene expression
There is considerable intellectual and organizational/departmental overlap in these fields that will fuel the synergy that has been a key feature of the UFGI and also ensures a healthy return on investment on faculty in these fields. Specifically, these research areas share a focus on downstream analysis of genomic and genetic data and an emphasis on the correlation of genotype with phenotype.
All fields are sufficiently young that UFGI can be competitive with other, more established genetics programs. The first three fields are primarily computer-based and, therefore, a small number of faculty members can have a great impact at minimal cost since large research laboratories are not necessary. Furthermore, many researchers on campus use methods from the first three areas but do not develop such methods meaning that hires in these areas will directly benefit the research programs of a disproportionately large part of the faculty.
Finally, the leadership of the College of Liberal Arts and Sciences, Health Science Center, Institute of Food and Agricultural Sciences and College of Engineering are already targeting new faculty hires to some of these areas demonstrating a university-wide appreciation and commitment.
Bioinformatics: The analysis of sequence or structure or expression data based on DNA sequences and the development of analytical tools to do so.
Bioinformatics merges the fields of biology, computer science, and information technology into a single discipline with three main subdivisions: the development of new algorithms and statistics with which to assess relationships in large datasets, the analysis and interpretation of nucleotide and amino acid sequences and protein structures, and the development and implementation of tools that enable efficient access and management of different types of information (excerpted from http://www.ncbi.nlm.nih.gov/Education).
Examples of questions addressed with Bioinformatics resources:
- Gene prediction and annotation
- Sequence similarity searching (identify gene families, functions, etc)
- Pairwise and multiple sequence alignments
- Protein classification and structure prediction
- Prediction of nucleic acid secondary structure
- Evolutionary relationships of organisms or genes (phylogenetics)
- Management and analysis of large datasets (sequences, microarrays, etc)
Comparative genomics: The comparative analysis of genes and gene functions across organisms with known phylogenetic relationships for the purpose of gene discovery and investigation. In addition to established model genomes (human, fly, worm, yeast, Arabidopsis, rice, various bacterial genomes), new genome models are needed for strategic taxonomic groups.
In plants, the strategic groups include the basal angiosperms, gymnosperms (e.g. pine), legumes, solanaceous species (tomato), and non-grass monocots. In animals, strategic groups include reptiles and lophotrochozoa. Novel and under-developed genome models provide new opportunities for genomics research initiatives that target evolutionarily and agriculturally important species.
In addition to sequence databases, strategic models require robust resources for functional analysis, e.g. forward and reverse genetics capabilities, facile transformation, ESTs and microarrays.
Examples of questions addressed with Comparative Genomics methods:
- Identification of genes shared across diverse organisms to gain insight into fundamental biological processes
- Microbial genetic models can provide essential platforms for functional analysis of eukaryotic genes
- Discovery of novel genes that are not shared between taxonomic groups provides identification of key, distinguishing structures or processes, e.g. disease resistance in plants
- Analysis of genetic variation to correlate with complex phenotypes, such as crop yield and stress tolerance
Population and statistical genetics: The use of computational and statistical methods to investigate the genetic basis of evolution in a population (population genetics) and to analyze and interpret genetic data (statistical genetics).
The completion of the Human Genome Project has resulted in a wealth of new data that must be carefully analyzed in order to reap the promised benefits of the project. It is meaningless to investigate the genetics of a single individual without first understanding the genetics of the entire population to which the individual belongs.
The field of population genetics focuses on evaluating the genetic diversity in a population and explaining that diversity in terms of the population’s unique evolutionary and demographic history. The field of statistical genetics, particularly that which focuses on the analysis of complex traits, is well positioned to play a key role in determining future research directions as the spotlight moves from sequencing projects to the interpretation of genetic datasets.
Researchers at UF are already developing new computational methods that include epistatic and additive interactions to more accurately model the way genes and gene products act in biological systems. Addition of new faculty in these two fields will directly benefit genetics researchers at UF who will have first access to more sophisticated methods as they are being developed on campus and also benefit the university as these methods are adopted by researchers worldwide.
Examples of questions addressed with Population Genetics methods:
- Analysis of genetic variation in a population
- Modeling of mutational and evolutionary mechanisms
- Detection of population structure
- Reconstruction of a population’s evolutionary history
- Analysis of recombinational hotspots and implications for haplophyte construction
- Power of different types of genetic markers to detect gene glow, selection, association/linkage, etc.
Examples of questions addressed with Statistical Genetics methods:
- Generally, genetic basis of complex traits
- Specifically, association of disease risk with specific genes or genetic variants
- Epigenetic effects on disease risk and other complex phenotypes
- Map of genetic variants to test individual’s disease risk
- Linkage of genetic variants/genetic map construction
- Analysis of genetic variation in a population
- Detection of population structure
Epigenetics: The study of mechanisms affecting the inheritance of genetic traits and/or patterns of genetic regulation that is not dependent primarily on the nucleotide sequence of the underlying DNA.
Classic examples of epigenetic systems include genomic imprinting, X chromosome inactivation, position effects, and paramutation. However, as the fundamental mechanisms responsible for these epigenetic systems come to light, the contemporary definition of epigenetics has evolved and broadened to encompass a wide diversity of research areas across all eukaryotic organisms and include topics such as gene regulation, differentiation and development, cancer, stem cell biology, RNA interference, nuclear transfer and embryo cloning, chromatin structure, gene therapy, nutrition and diet, nuclear compartmentalization and organization, DNA replication, etc.
A major underlying theme in epigenetics is that of gene regulation, particularly the regulation of transcription, and the most prominent mechanisms of epigenetic regulation involve chromatin structure and DNA methylation.
Examples of questions addressed with Epigenetic research:
- Role and mechanisms of DNA methylation in transcriptional regulation
- Mechanisms of chromatin remodeling and histone modification in gene regulation
- Mitotic and meiotic inheritance of patterns of gene expression
- Aberrant patterns of epigenetic regulation in cancer
- Polyploidy and regulation of gene expression
- Cloning and epigenetic remodeling of the genome in early embryogenesis
- Identification and characterization of the epigenome
Graduate Program in Genetics
The new Graduate Program in Genetics will serve to utilize the combined talents of the University of Florida faculty to offer a comprehensive genetics training program that will afford students unique opportunities and insights into fundamental aspects of genetics. As we face global challenges to agriculture, medicine, and society during the twenty-first century, the UFGI will broadly train students to participate in and lead the ongoing biological revolution to the benefit of society.
Applications of Genetics and Biotechnology
The recombinant DNA revolution of the 1970’s created renewed interest in genetics research, in particular as to how it could be applied to improve human life, and to meet the twin challenges of increasing food production and conserving natural resources without harming the environment. The hundreds of billions of dollars invested by the private and public sectors since then have begun to pay rich dividends in the form of powerful new drugs, the elucidation of the genetic basis of many diseases, gene therapy, improved food crops, and many other beneficial effects of these technologies on human health and the environment. It has also spawned the whole biotechnology industry. The four focal areas of research outlined above will further enhance the University of Florida’s current strengths in these technologies for the benefit of humankind.