Hao (Tony) Wu, Ph.D.
The Wallenberg Laboratory, Sahlgrenska University Hospital, University of Gothenburg
Bruna stråket 16, 413 45 Gothenburg, Sweden
My research: Past, Present and Future
Nothing in Biology Makes Sense Except in the Light of Evolution.
- Theodosius Dobzhansky, 1973
Curiosity of the unknown natural world is, indeed and will always be my motivation encouraging me constantly for further study on my way to scientific research. Although I’ve already asked and will continue to ask lots of naïve questions, the enthusiasm and persistence rooted deeply in my heart will definitely help me understand some of them.
Ever after I entered the university I began to realize that nothing can satisfy me unless I dedicated myself to be a scientist. However, in order to balance the stress of job hunt after graduation and my curiosity, I chose "Bio-Pharmaceutics" as my undergraduate major hoping that one day I could contribute to researches in Chinese traditional medicine as well as find a good job in pharmaceutical industry in near future. But in the second year of my college life an occasional opportunity attending to Prof. Hong-Yu Zhang’s presentation on “How to do scientific research” totally changed my so-called “science-and-job route”. There, for the first time, I heard the new emerged discipline "Bioinformatics" and its central role in biological science study. "Bioinformatics provides a whole new solution to scientific research and requires a better understanding both in biology and computer science as well as mathematics". Thereafter I was luckily to join Prof. Zhang's lab for some basic trainings in protein secondary structure prediction, antioxidant toxicity prediction, database construction and CADD (Computer-aided drug design). It is Prof. Zhang who guided and led me into the gate of scientific research. My first step towards evolution study was present in my undergraduate thesis on “The evolution of codon and amino acid usage biases”.
Four years of undergraduate study didn't satisfy much in my curiosity but on the contrary, opened “the Pandora box” of evolution. It seems that this leaves me only one option, namely my current graduate study, a five-year program to get my PhD degree supervised by Prof. Jun Yu and Song-Nian Hu at Zhejiang University. Prof. Yu and I talked many times and, based on my great interest in evolution, he thought I would be suitable to study a remaining unresolved question about diversification of bacterial replicative polymerases and their evolutionary roles underlying bacterial genome evolution. I mainly focused on four questions during this period: first, what's the relationship between GC content variation and DnaE2? second, what's the evolutionary role of PolC? third, how about the evolutionary order of these four polymerases(i.e.,DnaE1,DnaE2,DnaE3, and PolC)? fourth, is the diversification of DnaE polymerases related to environmental changes or host jumps?(Please see my recent publication for more details)
I really learned a lot during this five-year program pursuing my PhD degree, such as statistic analysis(by DPS/SPSS/R), data visualization(using Origin/Matlab/SVG/R), Perl programming, phylogenetic analysis, and some genome sequencing/mapping/assembling techniques, and also covered several famous books, including BIOLOGY: CONCEPTS AND CONNECTIONS (8th edition, by Rampbell et al.), LEHNINGER PRINCIPLES OF BIOCHEMISTRY (4th edition, by Nelson et al.), BROCK BIOLOGY OF MICROORGANISM (12th edition, by Martinko et al.), GENOMES III (2rd edition, by Brown et al.), GENE IX (9th edition, by Lewin et al.), GENETICS: FROM GENES TO GENOMES (3rd edition, by Goldberg et al.), MOLECULAR BIOLOGY OF THE CELL (5th edition, by Bruce et al.), etc. Undoubtedly, it is Prof. Yu who encouraged and drove me to keep curiosity, creativity, flexibility, passion, and willingness on my way to scientific research. What’s more, and perhaps one of the most important thing I ever learn in all these years is that by reading and digging into previous studies I begin to know some great scientists and their significant contributions to this field (partial scientists are listed below).
If I could do it all over again, and relive my vision in the twenty-first century, I would be a microbial ecologist." ----- E. O. Wilson
The next-generation sequencing technology (please see Loman et al. 2012 for review) has made the generating of big datasets possible for studying phylogenetic and taxonomic biogeography of various bacteria. Although bacteria are among the smallest forms of life, collectively they constitute the bulk of biomass on Earth and carry out many necessary chemical reactions for higher organisms which would never have evolved and sustained without these microorganisms. For example, genes from bacteria are reported to contribute to the survival and adaptation of plants (Schonknecht et al. 2013), insects (Husnik et al. 2013) and various mammals (Ley et al. 2008). In addition, the stability and variations of human microbiome (Spor, Koren, Ley 2011; Morgan, Segata, Huttenhower 2012; Faith et al. 2013) are also found to be associated with human development and physiology (Sommer, Backhed 2013). The altered microbial composition is also reported to contribute to the presence of invasive tumors/cancers (Kahrstrom 2012). What’s more, bacteria are abundant in various environments, such as soil (Fierer, Jackson 2006), marine (Venter et al. 2004; Ghiglione et al. 2012), and even in hyper-arid desert (Pointing et al. 2009). Thus, study of bacteria is considered the most fundamental of the biological sciences. But our understandings of these tiny organisms are still limited due to their enormous diversity and quantity as well as our inability to cultivate them in laboratory. Currently, major interests (see left figure) are mainly focusing on the following several aspects to which I’m also paying attention:
Basic genome features:
Bacterial genome DNA sequence variation and evolution (Nishida 2012); GC content variations (Wu et al. 2012); LeS vs. LaS (Wu et al. 2012); gene content and genome expansion (Konstantinidis, Tiedje 2004); prevalent genome streamlining of planktonic bacteria in the surface ocean (Swan et al. 2013); variation in global codon usage bias of bacteria is associated with their lifestyles (Willenbrock et al. 2006; Botzman, Margalit 2011); identification of plasmids (Brown Kav et al. 2012).
Biogeographic patterns and mechanisms (Martiny et al. 2006; Cohan, Perry 2007; Philippot et al. 2010; Burke et al. 2011; Hanson et al. 2012).
Core genes vs. flexible genes:
1) Flexible genes are important to niche partitioning and ecotype divergence owing to their immense gene functions involved in various metabolic pathways (Wiedenbeck, Cohan 2011; Grote et al. 2012);
2) HGTs contribute to genome expansion (Cordero, Hogeweg 2009; Treangen, Rocha 2011); trends and barriers of HGT (Popa, Dagan 2011); frequency of HGT (McDaniel et al. 2010); gene sharing and transfer network (Dagan, Artzy-Randrup, Martin 2008);
3) Common mechanisms of pathogenesis and symbiosis (Hentschel, Steinert, Hacker 2000); host jump and evolution of the pathogens (Lowder et al. 2009; Roulis, Polkinghorne, Timms 2012); genomics insights into prokaryote-animal symbioses (Moya et al. 2008);
4) The emergence time of de novo genes (David, Alm 2011); Selection-driven gene loss patterns in bacteria (Koskiniemi et al. 2012);
5) Environment-specific gene enrichments, e.g., carbohydrate-active enzymes in the human gut microbiota (Kaoutari et al. 2013), nondenitrifier nitrous oxide reductase genes in soils (Sanford et al. 2012);
6) Global transcriptome response to of soil bacterium to ionic liquid (Khudyakov et al. 2012); microbial community gene expression in ocean surface waters (Frias-Lopez et al. 2008);
7) Enzyme specificities and their regulation networks (Nam et al. 2012); phage-bacteria infection networks (Weitz et al. 2012); transcription regulation and environmental adaptation in bacteria (Cases, de Lorenzo, Ouzounis 2003).
Single cell genomics:
It is emerging as a powerful complement to cultivation-based and microbial community-focused research approaches (Stepanauskas 2012; Rinke et al. 2013).
1) Molecular phylogeny: pitfalls and progress (Moreira, Philippe 2000);
2) Gene tree vs. species tree (Doolittle 1999; Lerat, Daubin, Moran 2003);
3) Single-gene based (Woese, Fox 1977; Ludwig et al. 1998);
4) Multiple genes based (Brown et al. 2001; Brochier et al. 2002; Daubin, Gouy, Perriere 2002; Ciccarelli et al. 2006);
5) Genome-based (Qi, Luo, Hao 2004; Snel, Huynen, Dutilh 2005);
6) NJ vs. ML vs. Bayes;
7) Computational challenges due to large-scale dataset of bacterial genomes.
1) Human and health (Blaser, Falkow 2009; Maurice, Haiser, Turnbaugh 2013);
2) Biotechnology and bioremediation (Minty et al. 2013; Shi et al. 2013);
3) Synthetic biology.
1) The nature of the last universal ancestor and the root of the tree of life (Forterre et al. 1992); Early life on land and the first terrestrial ecosystems (Battistuzzi, Hedges 2009; Beraldi-Campesi 2013);
2) Evolution of multicellularity coincided with increased diversification of cyanobacteria and the great oxidation events (Schirrmeister et al. 2013).
- The mechanisms underlying bacterial high GC content variations and evolutionary implications;
- Diversification of Replicative DnaE polymerases;
- Environment pressures vs. bacterial gene regulation and expression;
- Bacterial land colonization;
- Gene tree vs. species tree;
- Strand-biased gene distribution and horizontal gene transfer in bacteria;
- Host/Environment-pathogen coevolution based on metagenomic studies;
- Origin of Mt and Cp;
- Ph.D., Bioinformatics (2007.9–2012.6): Advisor: Prof. Jun Yu and Prof. Songnian Hu; James D. Watson Institute of Genomics, Zhejiang University, China.
- B.S., Bioengineering (2002.9–2006.6): Advisor: Prof. Hongyu Zhang and Prof. Lingling Chen; Life Science School, Shandong University of Technology, Zibo, P. R. China.
- Postdoc (2014.11-present): Employer: Fredrik Backhed; University of Gothenburg,Sweden
- Research scientist (2012.6-2014.11): Employer: Zhang Zhang; Beijing Institute of Genomics, Chinese Academy of Sciences
- Research technician (2011.3-2012.3): Employer: Ibrahim S. Al-Mssallem; King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia.
- Data management (2006.6-2007.6): Shandong Toontian Information and Technology Co. Ltd., Zibo, P. R. China.
Adil Mardinoglu*, Hao Wu*, Elias Bjornson, Cheng Zhang, Antti Hakkarainen, Sari M. Rasanen, Sunjae Lee, Rosellina M. Mancina, Mattias Bergentall, Kirsi H. Pietilainen, Sanni Soderlund, Niina Matikainen, Marcus Stahlman, Per-Olof Bergh, Martin Adiels, Brian D. Piening, Marit Granér, Nina Lundbom, Kevin J. Williams, Stefano Romeo, Jens Nielsen, Michael Snyder, Mathias Uhlén, Goran Bergstrom, Rosie Perkins, Hanns-Ulrich Marschall, Fredrik Backhed, Marja-Riitta Taskinen, Jan Borén. An Integrated Understanding of the Rapid Metabolic Benefits of a Carbohydrate-Restricted Diet on Hepatic Steatosis in Humans 2018. Cell Metabolism. 559-571 Highlighted in Science Translational Medicine and Gut
Hao Wu, Eduardo Esteve, Valentina Tremaroli, Muhammad Tanweer Khan, Robert Caesar, Louise Mannerås-Holm, Marcus Ståhlman, Lisa M Olsson, Matteo Serino, Mercè Planas-Fèlix, Gemma Xifra, Josep M Mercader, David Torrents, Rémy Burcelin, Wifredo Ricart, Rosie Perkins, José Manuel Fernàndez-Real & Fredrik Bäckhed. Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug. Nature Medicine. 2017, doi:10.1038/nm.4345 Highlighted in Nature Reviews Gastroenterology & Hepatology and Cell Metabolism;
Hao Wu*, Valentina Tremaroli*, Fredrik Bäckhed. Linking Microbiota to Human Diseases: A Systems Biology Perspective. Trends in Endocrinology & Metabolism. 2015, DOI: j.tem.2015.09.011
Hao Wu, Yongjun Fang, Zhang Zhang, Jun Yu. The quest for a unified view of bacterial land colonization. ISME. 2014, doi: 10.1038/ismej.2013.247. My Summary;
Zhang Zhang,Jian Sang, Lina Ma, Gang Wu, Hao Wu, Dawei Huang, Dong Zou, Siqi Liu,Ang Li, Lili Hao, Ming Tian, Chao Xu, Xumin Wang, Jiayan Wu, Jingfa Xiao, Lin Dai, Ling-Ling Chen, Songnian Hu, and Jun Yu. RiceWiki: a wiki-based database for community curation of rice genes. Nucl. Acids Res. 2013, doi: 10.1093/nar/gkt926.
Ibrahim S. Al-Mssallem*, Songnian Hu*, Xiaowei Zhang*, Qiang Lin*, Wanfei Liu*, Jun Tan*, Xiaoguang Yu, Jiucheng Liu, Linlin Pan, Tongwu Zhang, Yuxin Yin, Chengqi Xin, Hao Wu, Guangyu Zhang, Mohammed M.Ba Abdullah, Dawei Huang, Yongjun Fang, Yasser O. Alnakhli, Shangang Jia, An Yin, Eman M. Alhuzimi, Burair A. Alsaihati, Saad A. Al-Owayyed, Duojun Zhao, Sun Zhang, Noha A. Al-Otaibi, Gaoyuan Sun, Majed A. Majrashi, Fusen Li, TALA, Jixiang Wang, Quanzheng Yun, Nafla A. Alnassar, Lei Wang, Meng Yang, Rasha F. Al-Jelaify, Kan Liu, Shenghan Gao, Kaifu Chen, Samiyah R. Alkhaldi, Guiming Liu, Meng Zhang, Haiyan Guo, and Jun Yu. Genome sequence of the date palm Phoenix dactylifera L. Nat. Commun. 2013, DOI: 10.1038/ncomms3274.
Hao Wu, Hongzhu Qu, Ning Wan, Zhang Zhang, Songnian Hu, Jun Yu. Strand-biased Gene Distribution in Bacteria Is Related to Both Horizontal Gene Transfer and Strand-biased Nucleotide Composition. Genomics, Proteomics & Bioinformatics, 2012,10(4):186-196.
Yongjun Fang*, Hao Wu*, Tongwu Zhang, Meng Yang, Yuxin Yin, Linlin Pan, Xiaoguang Yu, Xiaowei Zhang, Songnian Hu, Ibrahim S. Al-Mssallem, and Jun Yu. A complete sequence and transcriptomic analyses of date palm (Phoenix dactylifera L.) mitochondrial genome. PLoS ONE,2012,7(5): e37164(*co-first author).
Hao Wu, Zhang Zhang, Songnian Hu and Jun Yu. On the molecular mechanism of GC content variation among eubacterial genomes. Biology Direct, 2012, 7(1): 2.
Hong-Zhu Qu, Hao Wu, Tong-Wu Zhang, Zhang Zhang, Song-Nian Hu, Jun, Yu. Nucleotide compositional asymmetry between the leading and lagging strands of eubacterial genomes. Res. Microbiol. 2010, 161(10):838-46.
Hao Wu, Bin-Guang Ma, Ji-Tao Zhao, Hong-Yu Zhang. How similar are amino acid mutations in human genetic diseases and evolution? Biochem. Biophys. Res. Commun. 2007, 362: 233-237.
Hao Wu*, Yan Yang*, Sheng-Juan Jiang, Ling-Ling Chen, Hai-Xia Gao, Qing-Shan Fu, Feng Li, Bin-Guang Ma, and Hong-Yu Zhang. DCCP and DICP: Construction and Analyses of Databases for Copper- and Iron-Chelating Proteins. Geno. Prot. Bioinfo., 2005, 3:52–57 (*co-first author).
BIOLOGICAL VIEWPOINTS AND TECHNIQUES
My advisor used to tell me that ideas are more important than methods when I'm still a college student. But gradually I realized that methods are at least as important as ideas. Below I listed six viewpoints and a dozen of specific techniques we should care about (will be updated continually):
- Six viewpoints:
Comparative analysis; Association study; Population genetics; Systematic research; Ecological perspective; Experimental evolution.
- Specific techniques:
Gene knock in and knock out (gene therapy); artificial mutation; Structure determination - X-ray and NMR; Genome sequencing (plus RNA-seq, metagenomics); CHIP-seq; Proteomics techniques; Computer programming - Perl and Python; Data visualization - R; Phylogenetic analysis; Network construction - PPI and metabolic pathway associated; Scanning electron microscope; Statistical inference.
- Skills development for graduate study:
Online courses and lectures: Khan Academy iBiology edx; Coursera; Academic Earth; The OpenCourseWare Consortium; Videolectures; iBioSeminars; JoVE; WEB of STORIES; Genetic Science Learning Center at the University of Utah; HHMI BioInteractive; TED.
Resources for microbiology: Microbesonline; CAMERA; MG-RAST; IMG@DOE's Joint Genome Institute (JGI); EBI metagenomics; NIH human Microbiome Project Data Analysis and Coordination Center(DACC); NCBI microbial genomes; NCBI Taxon identifier; NCBI batch download; GOLD; Systems Biology Markup Language (SBML).
- Notes:In the field of Microbiology, Evolution, DNA Replication and Mutation
- Notes:In alphabetical order
NOBEL LAUREATES IN MOLECULAR MICROBIOLOGY
- Notes: Cited from 'BROCK BIOLOGY of MICROORGANISMS(13th Edition)'
|George Beadle and Edward Tatum;1941
Max Delbruck and Salvador Luria;1943
Joshua Lederberg;1946 and 1952
James Watson, Francis Crick and Maurice Wilkins;1953
Francois Jacob, Jacques Monod and Andre Lwoff;1959
Marshall Nirenberg, Robert Holley and H. Gobind Khorana;1966
Howard Temin, David Baltimore, and Renato Dulbecco;1969
Hamiltn Smith, Daniel Nathans, and Werner Arber;1970
J. Michael Bishop and Harold Varmus;1972
Fred Sanger;1958 and 1977
Carl Woese;1977 and Crafoord Prize in 2003
Sidney Altman and Thomas Cech;1981
Barry Marshall and Robin Warren;1982
Luc Montagnier, Francoise Berre-Sinoussi and Harald Zur Hausen;1983
Andrew Fire and Craig Mello;1998
GIANTS of THE EARLY DAYS of MICROBIOLOGY
- Notes: In chronological order
- Notes: Cited from 'BROCK BIOLOGY of MICROORGANISMS(13th Edition)'
Antoni van Leeuwenhoek