The Weitz group is interested in the structure and dynamics of complex biological systems. The primary mission is to understand how viruses transform human health and the fate of our planet.
The research group includes physicists, computational biologists, mathematicians, and bioinformaticians working on three major research themes: (i) viral dynamics at the molecular, population and evolutionary scales; (ii) theoretical ecology and evolutionary biology; (iii) disease dynamics and epidemiology. The work in the Weitz group is primarily theoretical/computational in nature, and utilizes the tools of nonlinear dynamics, stochastic processes, and large-scale data analysis to interact with experimentalists.
Examples of recent and ongoing projects include studies of viral-host infection networks, dynamics of complex viral-host communities, the spread and control of infectious diseases, and the link between game theory and strategic behavior of viruses and microbes.
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.
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.
Neuroscience, neural engineering, human augmentation, human-robot interaction, rehabilitation, sport science
Physiological and biomechanical mechanisms underlying fine motor skills and their adjustments and adaptations to heightened sympathetic nerve activity, aging or inactivity, space flight or microgravity, neuromuscular fatigue, divided attention, and practice in humans. He uses state-of-the-art techniques in neuroscience, physiology, and biomechanics (e.g., TMS, EEG, fMRI, single motor unit recordings, microneurography, mechanomyography, ultrasound elastography, and exoskeleton robot) in identifying these mechanisms.
Using yeast Saccharomyces cerevisiae as a model, my laboratory investigates molecular mechanisms underlying eukaryotic genome stability. Chromosomal rearrangements create genetic variation that can have deleterious or advantageous consequences. Karyotypic abnormalities are a hallmark of many tumors and hereditary diseases in humans. Chromosome rearrangements can also be a part of the programmed genetic modifications during cellular differentiation and development. In addition, gross DNA rearrangements play a major role in chromosome evolution of eukaryotic organisms. Therefore, elucidation of molecular mechanisms leading to chromosome instability is important for studying the human pathology and also for our understanding of the fundamental processes that determine the architecture and dynamics of eukaryotic genomes.
My overall contribution to the field of genome instability has been the demonstration of the phenomenon that repeats often found in higher eukaryotic genomes including the human genome are potent sources of double-strand breaks (DSB) and gross chromosomal rearrangements (GCR). Specifically, my lab, is investigating how repetitive sequences that can adopt non-B DNA secondary structures pose a threat to chromosomal integrity dictated by their size and arrangement. Currently three sequence motifs are studied in my laboratory: inverted repeats; Friedreich’s ataxia GAA/TTC trinucleotide repeats and G-quadruplex-forming tracts. We also are collaborating with Dr. Malkova lab, University of Iowa, to study one of the outcomes of the DSB formation at unstable repeats – break-induced replication.
Research in our laboratory focuses on a class of intracellular ion channels know as ryanodine receptors (RyRs). In mammals, there are three RyR isoforms. RyR1 and RyR2 are the predominate isoforms in skeletal and cardiac muscle, respectively where they are the primary efflux pathway for the release of calcium from the sarcoplasmic reticulum to activate contraction. RyR3 has a wide tissue distribution and contributes to calcium regulation in a variety of cell types. RyRs are the largest known ion channel and are regulated by a multitude of endogenous effectors, including ions, metabolites and regulatory proteins. Therefore, an area of interest is the regulation of these RyR channels by endogenous effectors; especially as it relates to altered contractile function associated with cardiac and skeletal disease, skeletal muscle fatigue and aging. We analyze channel function on multiples levels of organization. Sarcoplasmic reticulum vesicle [3H]ryanodine binding is used to examine large populations of channels. Individual channels are incorporated into artificial lipid bilayers in order to record single channel currents and assess channel kinetics. Calcium release from permeabilized muscle fibers provides a method of examining RyR function in situ. My research has two long-range goals. The first is to understand how intracellular calcium is regulated and how alterations in the regulation effects cell function. The second goal is to understand the RyR regulatory sites that could potentially be exploited for the development of pharmacological compounds to treat disorders of cellular calcium regulation.