Prof. Zhongying ZHAO
Professor, Department of Biology
- SYSTEM HEALTH and ETHICAL AND THEORETICAL AI
Professor Zhongying Zhao obtained his BSc and MSc at the Department of Biology from Anhui Normal University and Beijing Normal University in Anhui and Beijing China, respectively. He earned his PhD from the Department of Molecular Biology and Biochemistry at Simon Fraser University in BC, Canada. Prior to joining the University in 2010, he did his postdoc in the Department of Genome Sciences at the University of Washington, Seattle, WA, USA for 5 years.
His research activities are mainly funded by Hong Kong Research Grant Council (RGC). As a PI, he has secured seven RGC grants to support his research, including five General Research Funds (GRFs), one NSFC/RGC Joint Research Scheme fund and one Early Career Scheme (ECS) project since 2011. He has established wide collaborations both locally, regionally and internationally, which helped him win RGC Collaborative Research Fund as a Principle coordinator (PC). His research mainly focuses on three topics, which are summarized below.
Application of cutting-edge genomic technologies in genome assembly, genome finishing and annotation
Existing genomes of various species have been produced mainly with Next Generation Sequencing (NGS) technology. The relatively short read length associated with NGS prevents generation of a high quality of genome assembly, especially in terms of continuity, leaving most genome drafts as fragmented pieces called contigs. This is mostly contributed by the presence of repetitive sequences. Third Generation Sequencing Technologies, including Single Molecule Real-Time (SMRT) Sequencing from PacBio and long-read sequencing from Oxford Nanopore Technologies, provide an opportunity for de novo genome assembly of high continuity, genome finishing and improvement in genome annotation. We have applied these technologies mostly in C. elegans and its related species, C. briggsae to improve their existing genome assembly and annotation, which are used for subsequent comparison and functional characterization.
Mechanism of postzygotic hybrid incompatibilities between nematode species
Hybrid incompatibility (HI), including sterility and lethality between closely related species, was noticed over a century ago, but only recently is it possible to decipher the molecular basis of HI. However, C. elegans has not been utilized for such research because lack of a sister species with which it can mate and produce hybrid viable progeny. C. briggsae is a close relative of C. elegans. His team tries to understand the molecular mechanisms of hybrid incompatibility using C. briggsae and its newly isolated sister species, C. nigoni, as a model.
Gene regulatory networks underlying cell fate determination during nematode embryogenesis
During C. elegans embryogenesis, the developmental potential of its fertilized egg is restricted in a stepwise manner following each cell division by differentially expressing a cohort of regulatory proteins. Empowered by automated lineaging together with genetic and genomic tools, his team aims to understand the gene regulatory network underlying the tissue/organ formation during embryogenesis.
1. Identification of novel transcripts using direct RNA sequencing
Statistics of the newly identified isoforms with Nanopore Direct RNA Sequencing in C. elegans. (A) Summary of the isoforms called using long reads. Left: Bar plots of the number of existing isoforms that are recovered (black) or uncovered (gray). Right: Bar plots of the number of novel isoforms called by TrackCluster. (B,C) Abundance (B) or length distribution (C) of the novel isoforms of various categories. (D) Count of the isoforms output by TrackCluster (gray), existing isoforms (yellow), and their ratio (blue) over read length, in nt. (E) An example of TrackCluster predicted isoforms. Shaded in blue is the accumulative long read coverage of unc-52 in all developmental stages. Shaded in gray are three novel isoforms (colored in red or green as in B) supported by the highest read coverage along with the existing isoforms (black) to which they bear the highest similarity. Genomic coordinates are shown at the top, in kb. Published in Genome Research 2020 (doi: 10.1101/gr.251512.119).
2. Genome improvement with third generation sequencing
Comparison of synteny consisting of gene blocks between C. briggsae and C. nigoni or C. elegans. A total of 15,157 and 7,679 orthologous gene pairs were used for comparison between C. briggsae and C. nigoni or C. elegans, respectively, with a bin size of 30 genes. (A) Syntenic view. (B and C) Dotplot view. Gene count is indicated on each axis along with its associated chromosome (differentially color coded). Published in Nucleic Acids Research 2018. doi: 10.1093/nar/gkx1277