It is our vision that one day mathematics and computation will be capable of reliably predicting, manipulating and optimizing biomedical systems for the advancement of medicine, drug development, biotechnology and productive and sustainable stewardship of the environment.
Pursuing this vision, the goal of our lab is to understand small biological systems in great detail. We work toward this goal by performing studies that target the fine-tuned synergism between genes, proteins and metabolites, and investigate the resultant, usually very effective functioning of healthy cells and organisms in comparison to those that are mutated or diseased. Milestones along the way are insights into the rationale for the intricate design and operation principles that govern biological systems.
The work in our lab is strictly mathematical and computational, but we collaborate with several superb experimental groups that provide us with data and appreciate our modeling efforts as tools for explanation and hypothesis generation.
Cichlid fishes from Lake Malawi offer the unprecedented opportunity to study the relationship between genotype and phenotype in wild vertebrates. Over the past ten years, with funding from the Alfred P. Sloan Foundation, NSF and NIH, we’ve pioneered genomic and molecular biology approaches in this natural system to solve problems difficult to address in traditional model organisms. Major projects include (i) tooth and taste bud patterning and regeneration; (ii) genomics of complex social behavior; and (iii) developmental diversification of the cranial neural crest, placodal plate and neural plate. We analyze and manipulate genomes and development in multiple species of Malawi cichlids, spanning divergence in embryonic/adult phenotypes and behavior – and translate our findings to zebrafish and mouse models.
Sociobiology, behavior, molecular evolution, genomics, evolutionary biology, bioethics, population genetics
The evolution of sociality represented one of the major transition points in biological history. I am interested in understanding how evolutionary processes affect social systems and how sociality, in turn, affects the course of evolution. My research focuses on the molecular basis underlying sociality, the nature of selection in social systems, the breeding biology of social animals, the process of self-organization in social groups, and the course of development in social species.
In the McDonald lab, we are taking an integrated systems approach to the study of cancer. This means that we view cancer not as a defect in any particular gene or protein, but as a de-regulated cellular/inter-cellular process. An understanding of such complex processes requires the implementation of experimental approaches that can provide an integrative holistic or 'systems' view of intra-and inter-cellular process. We employ a number high-throughput genomic (e.g., DNA-seq, RNA-seq, microarray) technologies to gather systems data on the status of cancer cells. We strive to integrate into our research program, the exceptional strengths that exist at Georgia Tech in the fields of engineering and the computational sciences.
Our current goals are: 1) development of a generalized cancer diagnostic using mass spectrometric metabolic profiling; 2) development of small non-encoding RNAs as potential therapeutic agents and the use of functionalized nanoparticles (nanohydrogels) for their targeted delivery to cancer cells; and 3) exploring the significance of mRNA splice variants in the onset and progression of cancer.
We are broadly interested in evolutionary genomics and epigenomics problems and have never been afraid to take up a new topic. Here are some of our current research interests.
Epigenetic Evolution of human Brains: A major research thrust in the lab is to understand how epigenetic regulatory mechanisms evolve. One specific question is how DNA methylation patterns in human brains have evolved since humans and chimpanzees have diverged. Human brains are arguably one of the most exceptionally rapidly evolved organ in the human body. We have published a few articles on this, and hopefully many more to come.
Neuroepigenomics: We are also interested in understanding how epigenetic marks regulate and/or propagate neuropsychiatric diseases of human brains. Our current research include epigenetic analysis of schizophrenia brains.
Epigenetics and Genome Evolution: Epigenetic mechanisms are widespread throughout the tree of life, but its components and how each component interact with each other vary greatly across different taxa. For example, genomic patterns of DNA methylation in invertebrate animals differ greatly from those of vertebrates. We have been studying how DNA methylation in invertebrates vary across the genome and among species, and how epigenetic variation yields functional consequences.
Linking genomes and phenotypes in a vertebrate model system: In collaboration with Dr. Donna Maney at Emory University, we are investigating how a prevalent chromosomal polymorphism in the white-throated sparrow leads to two distinctive and complex phenotypes. We use genomic and epigenomic tools to complement the behavioral and physiological approaches of our collaborators.
Platt Lab Mission: To fuse engineering, cell biology, and physiology to understand how cells sense, respond, and remodel their immediate mechanical and biochemical environments for repair and regeneration in health and disease, then to translate that knowledge to clinics domestically and internationally to address global health disparities.
We study folding and structure of RNA and DNA as modulated by sequence, covalent damage, anti-cancer drugs, proteins, other nucleic acid molecules. The oldest assembly in biology is the ribosome, which is a primary focus of our efforts. Ancient ribosomal structure and function, from beyond the root of the tree of life, can be inferred from extant structure/function combined with phylogeny, evolutionary theory, biophysical chemistry, bioinformatics and molecular biology. We use all of these approaches to construct models of ancient ribosomes, which we then study by biochemical methods. Three-dimensional structure, being more conserved over evolutionary time than sequence, offers some of the most important guideposts in our journeys down the base of the tree of life.
Yeast genetics and molecular biology, chaperones and protein misfolding, amyloid and prion diseases, epigenetics and protein-based inheritance.
My laboratory employs yeast models to study prions and amyloids. Prions were initially identified as proteins in an unusual conformation that cause infectious neurodegenerative diseases, such as "mad cow" disease, kuru or Creutzfeldt-Jakob disease. Infection depends on the prion's ability to convert anon-prion protein, encoded by the same host maintenance gene, into the prion conformation. Prions form ordered cross-beta fibrous aggregates, termed amyloids. A variety of human diseases, includingAlzheimer's disease, are associated with amyloids and possess at least some prion properties. Someamyloids have positive biological functions. Many proteins can form amyloids in specific conditions. It is thought that amyloid represents one of the ancient types of the protein fold. Some yeast non-Mendelianheritable elements are based on a prion mechanism. This shows that heritable information can be coded in protein structures, in addition to information coded in DNA sequence. Therefore, prions provide a basis for the protein-based inheritance in yeast (and possibly in other organisms).
Major topics of research in my lab include cellular control of prion formation and propagation (with a specific emphasis on the role of chaperone proteins), and development of the yeast models for studying mammalian and human amyloids, involved in diseases. Our research has demonstrated that prions can be induced by transient protein overproduction and discovered the crucial role of chaperones in prionpropagation, shown evolutionary conservation of prion-forming properties, established a yeast system for studying species-specificity of prion transmission, and uncovered links between prions, cytoskeletalnetworks and protein quality control pathways.
Develop microneedle patches for vaccination that is simpler and more effective than conventional injection.
Design microneedle patches for rapid and slow-release delivery of drugs.
Translate microneedle technology from the laboratory into human clinical studies and advanced manufacturing.
Study targeted drug delivery to the eye using microneedle injection into the suprachoroidal space.
Examine the effects of laser-activated nanoparticles on delivery of molecules into cells to manipulate cellular behavior
Dr. Prausnitz and his colleagues carry out research on biophysical methods of drug delivery, which employ microneedles, ultrasound, lasers, electric fields, heat, convective forces and other physical means to control the transport of drugs, proteins, genes and vaccines into and within the body. A major area of focus involves the use of microneedle patches to administer vaccines to the skin in a painless, minimally invasive manner that improves vaccine effectiveness by targeting delivery to the skin’s immune cells. In collaboration with Emory University, the Centers for Disease Control and Prevention and other organizations, Dr. Prausnitz’s group is advancing microneedles from device design and fabrication through pharmaceutical formulation and preclinical animal studies through studies in human subjects. In addition to developing a self-administered influenza vaccine using microneedles, Dr. Prausnitz is translating microneedles technology especially to make vaccination in developing countries more effective.