47 research outputs found
Genetic Control of Root Development in Arabidopsis
The development of the root system represents an important feature of plant development,
as the root is the site of water and nutrient uptake, it anchors the plant in the soil, and is a
site of interaction with other organisms, which may be pathogenic (such as nematodes) or
beneficial (such as mycorrhiza). The model organism Arabidopsis thaliana is an excellent
model to study the genetic basis of root development, and to study the control of gene
expression in response to hormones and as mediators of hormone action. A key question in
developmental biology is how genes and hormone signalling systems interact to control cell
identity, cell division, cell patterning and cell differentiation. To address this, the work
described in this thesis focused of two genes, previously identified as playing important roles
in root development - the POLARIS (PLS) gene, which encodes a 36 amino acids peptide; and
MERISTEM-DEFECTIVE (MDF), which encodes an SR protein. In the course of this work,
information on the pathways influenced by each gene was determined using high resolution
RNA profiling followed by bioinformatics analysis, and information was used to identify
pathways in which the two genes are involved. The results obtained show that PLS is
required for both correct ethylene signalling and, independently, auxin biosynthesis in
response to ethylene; and PLS exerts its effect via control of the tryptophan-independent
pathway for auxin biosynthesis. It is also shown that MDF is a likely splicing factor, required
for the regulation of auxin pathway genes and transcription factors expressed in the root
meristem via the control of alternative splicing - it likely controls the balance in the
meristem between stem cell identity and differentiation. The results provide new insights
into the genetic and molecular mechanisms by which these genes regulate hormone
signalling pathways to in turn control the development of the Arabidopsis root
HUMAN BOCAVIRUS 1 GENOME ORGANIZATION AND REPLICATION MECHANISM
Human bocavirus is a human pathogen that was identified in 2005. For the past decade, most of the studies about this virus were focused on clinical detection and its association-with diseases, while very little was known about the molecular virology. The studies presented in this thesis are composed of three parts: 1) Identification of novel HBoV1 proteins by transfection of an HBoV1 infectious clone or during HBoV1 infection; 2) exploring the interactions between the viral genome and proteins to uncover the details underlying HBoV DNA replication; and 3) providing evidence of HBoV1 hairpin independent DNA replication. In the first study, we identified three new non-structural proteins of human bocavirus 1 during infection of polarized human airway epithelium. Of the three newly identified proteins, we proved that one non-structural protein is critical for virus replication in the polarized human bronchial airway epithelium. The creation of a non-replicating infectious HBoV1 mutant may have particular utility in vaccine development for this virus. In the second study, we identified both cis- and trans-acting proteins that are required for HBoV1 DNA replication at the right-end hairpin in HEK293 cells. We also localized the minimal replication origin to a 46-nt sequence in the right-end hairpin, which contains both NS1 nicking and binding sites. The identification of these essential elements of HBoV1 DNA replication acting both in cis and trans provides opportunities for developing antiviral strategies targeting HBoV1 DNA replication, and to design next generation recombinant HBoV1 vectors, a promising tool for gene therapy of lung diseases. In the third study, we provided evidence that HBoV1 could replicate independent of hairpin sequence, which is quite different from other parvoviruses. Although the mechanisms are not fully understood, this study opened new directions for future studies of parvoviruses
Inverse Game Theory for Stackelberg Games: the Blessing of Bounded Rationality
Optimizing strategic decisions (a.k.a. computing equilibrium) is key to the
success of many non-cooperative multi-agent applications. However, in many
real-world situations, we may face the exact opposite of this game-theoretic
problem -- instead of prescribing equilibrium of a given game, we may directly
observe the agents' equilibrium behaviors but want to infer the underlying
parameters of an unknown game. This research question, also known as inverse
game theory, has been studied in multiple recent works in the context of
Stackelberg games. Unfortunately, existing works exhibit quite negative
results, showing statistical hardness and computational hardness, assuming
follower's perfectly rational behaviors. Our work relaxes the perfect
rationality agent assumption to the classic quantal response model, a more
realistic behavior model of bounded rationality. Interestingly, we show that
the smooth property brought by such bounded rationality model actually leads to
provably more efficient learning of the follower utility parameters in general
Stackelberg games. Systematic empirical experiments on synthesized games
confirm our theoretical results and further suggest its robustness beyond the
strict quantal response model
Structure of the NS1 Protein N-Terminal Origin Recognition/Nickase Domain from the Emerging Human Bocavirus
This is the publisher's version, also available electronically from http://www.asm.org/Human bocavirus is a newly identified, globally prevalent, parvovirus that is associated with respiratory infection in infants and young children. Parvoviruses encode a large nonstructural protein 1 (NS1) that is essential for replication of the viral single-stranded DNA genome and DNA packaging and may play versatile roles in virus-host interactions. Here, we report the structure of the human bocavirus NS1 N-terminal domain, the first for any autonomous parvovirus. The structure shows an overall fold that is canonical to the histidine-hydrophobic-histidine superfamily of nucleases, which integrates two distinct DNA-binding sites: (i) a positively charged region mediated by a surface hairpin (residues 190 to 198) that is responsible for recognition of the viral origin of replication of the double-stranded DNA nature and (ii) the nickase active site that binds to the single-stranded DNA substrate for site-specific cleavage. The structure reveals an acidic-residue-rich subdomain that is present in bocavirus NS1 proteins but not in the NS1 orthologs in erythrovirus or dependovirus, which may mediate bocavirus-specific interaction with DNA or potential host factors. These results provide insights into recognition of the origin of replication and nicking of DNA during bocavirus genome replication. Mapping of variable amino acid residues of NS1s from four human bocavirus species onto the structure shows a scattered pattern, but the origin recognition site and the nuclease active site are invariable, suggesting potential targets for antivirals against this clade of highly diverse human viruses