UFGI Strategic Plan

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.