The ultimate goal of my research is to understand viruses and viral diseases for the betterment of agriculture. Our research involves a number of important viruses that infect plants, which include Grapevine rupestris stem pitting-associated virus (GRSPaV), a ubiquitous and important pathogen of grapes worldwide. Current research directions include: Processing and subcellular localization of polyproteins; structure and cellular localization of viral replication complexes; evolution and bio-informatics of grapevine viruses; development of virus-induced gene-silencing vectors ; and, development and application of technologies for the diagnosis of grapevine viruses.Learn More
A key focus of the group is on the protein degradation machinery that helps to maintain proper level of proteins (protein homeostasis) in Mycobacterium tuberculosis, the causative agent of TB, the world's single largest infectious killer that is annually responsible for 1.5 million deaths. The questions we aim to answer are:
1) What is the assembly mechanism of the M. tuberculosis proteasome core particle and its regulatory particles?
2) What is the role of allostery and long-range interactions in the machinery that tags substrates for proteasomal degradation?
3) How are substrates selected for tagging and degradation?
4) What is the molecular basis of antibiotics that operate by disrupting proteasomal protein degradation?
Many of the signaling pathways that are involved in development are also involved in the onset and progression of disease. As an example, the Wnt signaling pathway is required during many stages of development and in the homeostasis of stem cells in the adult. Perturbation of this pathway in stem cells in the adult often leads to cancer. It is now known that greater than 90% of colorectal cancers are caused by mutations in the Wnt signaling pathway. As this pathway is important for both proper development and disease, I am curious to know how this pathway can turn it self on and off so many times during development and why it fails to turn off in disease. The lab focuses on two negative feedback regulators of Wnt signaling: Nkd1 and Axin2.Learn More
My lab aims to understand 1) the molecular genetic mechanisms of recombination in mammalian cells; 2) how defects in recombination contribute to tumorigenesis; and, 3) the nature of recombination hotspots. We are presently researching questions pertaining to: the mechanism and frequency of recombination in mammalian cells; the role of large palindromes in promoting recombination; mammalian heteroduplex DNA formation and repair; genetics of strand invasion and 3' end polymerization; how DNA sequences act to stimulate recombination; non-crossover mechanisms of homologous recombination; the genetic control of recombination.Learn More
As they are literally rooted in place, plants possess remarkable mechanisms that perceive, interpret, and respond to internal and external cues so as to optimise plant growth and development relative to prevailing environment conditions. Despite the incredible diversity in plant forms, the molecular mechanisms that control plant responses to internal and external cues are highly conserved across diverse genera. The timing and localisation of these mechanisms shape plant and development. Our research team aims to gain greater insights into molecular mechanisms that plants employ to convert internal cues and external signals into appropriate adjustments in resource acquisition and allocation, focusing on the role of gene regulation in conditioning these adjustments.Learn More
My lab examines the control mechanisms underpinning starch biosynthesis in leaf chloroplasts (which make starch during the daytime, and degrade it at night) of the model plant Arabidopsis thaliana, and non-photosynthetic amyloplasts of cereal endosperms such as maize, wheat, barley and rice which make storage starches. More specifically, we are interested in the biochemical control mechanisms governing the many enzymes and enzyme classes which make up the core pathway of starch biosynthesis. This involves investigating the role of protein-protein interactions and protein phosphorylation in coordinating the proteins involved in starch synthesis and degradation within the plastid to produce the highly ordered and complex structure of the starch granule.Learn More
To better study the biology and virulence of fungal pathogens, we are developing new genomic technology platforms for diverse fungal species. We are exploiting CRISPR-Cas9 based technologies to revolutionize the way we do high-throughput functional genomic analysis in fungal pathogens. This is enabling us to map large-scale genetic interaction networks, and uncover genetic factors and pathways that mediate important phenotypes associated with pathogenesis, antifungal drug resistance, and other biological processes associated with fungal infectious diseases.Learn More
First, we have systematically generated inhibitors and activators for E3 ubiquitin ligases to discover new enzyme catalytic mechanism and new substrates. We continue to develop synthetic peptides and proteins to delineate biochemical mechanisms of E3 ubiquitin ligases.
Second, we showed that structure-based protein engineering enables development of anti-viral reagents for Middle East respiratory syndrome (MERS) coronavirus. Now we started engineering post-translational modifications to probe and rewire DNA damage signaling for cancer therapeutics.
Finally, we created molecular tools to increase CRISPR-Cas9 genome-editing efficiency. Now we are developing new tools as "off-switch" for CRISPR-based gene editing through targeted protein degradation.
The Cox lab aims to gain a better understanding of the molecular underpinnings of resistance mechanisms. Specifically, we study bacterial efflux systems, which will provide insight into their physiological functions and origins and will also support future drug discovery efforts and antibiotic stewardship. In addition, recognizing the need for innovation in the search for new antibacterial agents, we are exploring novel approaches to control bacterial infections by investigating the inhibition of bacterial adhesion to host cells.Learn More