General

Dr. Gaowen Liu

Principal Investigator

The Liu lab systematically studies genomic plasticity. We use budding yeast and fission yeast as model systems in the lab to study their genomic instability and adaptive behavior. We aim to understand how the cells evolve to adapt to extreme internal and external changes through genomic changes.

Research Areas

  1. Developing single cell sequencing and lineage analysis to systematically analyze genomic changes to the deletion of evolvable genes;
  2. Genome interplay between synthetic yeast chromosomes and wild type chromosomes during evolution;
  3. Develop multi-CRISPR mediated Schizosaccharomyces pombe chromosomes synthesis

Education

2016-2020 Postdoc, University of Lausanne, Switzerland

2013–2016 PhD, Molecular biology (Genomics and systems biology) Nanyang Technological University, Singapore 

​2010–2012 MS, Biology (Molecular biology) National University of Singapore, Singapore 

2006–2010 BS, Biology (Animal Science) Huazhong Agricultural University, China

Experience

Gaowen Liu received her Master degree in 2012 from National University of Singapore (NUS) for her study of epigenetic regulation of FLC locus in Arabidopsis of Dr. Yuehui He at the Temasek life science Laboratory (TLL).  She then joined the group of Dr. Giulia Rancati at Institute of Medical biology, A*STAR to systematically study adaptive evolution of budding yeast to the deletion of essential genes, where she published first author paper in Cell and received her PhD in 2016 from Nanyang Technological University in Singapore. She obtained postdoctoral training in the laboratory of Prof. Sophie Martin at University of Lausanne in Switzerland, studying fusion efficiency evolution to the deletion of essential mating genes. She received prestigious Long-term postdoctoral fellowship from Human Frontier Science Project (HFSP) for her postdoctoral training. She won Ray Wu prize, national excellent oversea student award and Kaluza prize finalist in 2016. She became a PI in SIAT since 2021

Publications

  • Liu G, Yong M, Yurieva M, K. G. Srinivasan, Liu J, Lim J, Poidinger M, Wright G, Zolezzi F, Choi H, Pavelka N, Rancati G. Gene essentiality is a quantitative property linked to cellular evolvability. Cell. 2015 163(6):1388-99       
  • Liu G, Rancati G. Adaptive Evolution: Don’t Fix What’s Broken. Current Biology. 2016 Volume 26, Issue 4, Pages R169-R171                   
  • Camattari A, Goh A, Yip LY, Tan AH, Ng SW, Tran A, Liu G, Liachko I, Dunham MJ, Rancati G. Characterization of a panARS-based episomal vector in the methylotrophic yeast Pichia pastoris for recombinant protein production and synthetic biology applications. Microb Cell Fact 15, 139 (2016)   
  • Huber RG, Kulemzina I, Ang K, Chavda AP, Suranthran S, Teh JT, Kenanov D, Liu G, Rancati G, Szmyd R, Kaldis P, Bond PJ, Ivanov D. Impairing Cohesin Smc1/3 Head Engagement Compensates for the Lack of Eco1 Function. Structure. 2016 24(11):1991-1999                                        
  • Vjestica A, Marek M, N’kosi P, Merlini L, Liu G, Berard M, Billault-Chaumartin I, Martin SG. A toolbox of Stable Integration Vectors (SIV) in the fission yeast Schizosaccharomyces pombe. Journal of Cell Science. 2020 133: jcs240754     
  • Vjestica A, Bérard M, Liu G, Merlini L, N’kosi P, Martin SG. Cell cycle-dependent and independent mating blocks ensure fungal zygote survival and ploidy maintenance. PLOS Biology .2021

Research Interests

Gene essentiality is a quantitative trait

We screened ~1000 reported essential gene and found ~9% of them can be deleted from the genome without leading to lethality of the cell. We renamed these 88 genes as evolvable genes to distinguish them from non-essential genes and non-evolvable essential genes. Our finding revealed that gene essentiality is not a qualitative black/white trait but a quantitative trait linked to cellular evolvability.

Aneuploidy suggested adaptive mechanism

We analyzed more than 600 strains carried an evolvable gene deletion and discovered that the vast majority are aneuploid. These cells displayed different kinds of large scale genomic changes: whole genome duplication, disomy in haploids, monosomy in diploids, heterogeneous genome composition, etc. These observation suggested that these cells survived extreme stress- “essential gene deletion”- through aneuploidy.

Evolvable genes form a continuum in between non-evolvable essential genes and non-evolvable genes. 

We analyzed the conservation score/ network topology properties of the three class of genes: non-essential genes, evolvable genes, non-evolvable essential genes.  We found that evolvable genes always positioned in between the other two classes.          

Evolvable genes were enriched in protein complexes involved in intracellular trafficking. Interestingly independently generated mutant strains carry the same gene deletion or deletion of genes involved in the same protein complex carried specific set of aneuploidies, suggesting that aneuploidy could function as an adaptive mutations and that cells respond to inactivation of different component of the same functional submodule in similar ways. Accordingly we showed that the presence of either specific aneuploidies or a specific gene on the aneuploid chromosome was required and sufficient to bypass the lethality of genes belonging to the same functional module.

Conferences

• Flash Talk: Investigate genetic basis of S.pombe mating preference. IBaselLife, Basel, Switzerland, 10-13 Sep, 2017 

• Talk: Adaptive evolution to the deletion of essential genes. Cell Biology 2016 ASCB annual meeting. San Francisco, US, 3-7 Dec, 2016 

• Talk: Adaptive evolution to the deletion of budding yeast essential genes. 5th Annual Sc2.0 and Synthetic Genomes Conference. Edinburgh, UK, 7-9 Jul, 2016 

• Talk W12-3: Genetic, genomic and systems biology analysis of adaptive evolution of budding yeast to the deletion of essential genes. 27th International conference on yeast genetics and molecular biology. Levico Terme, Italy, 6–12 Sep, 2015. 

• Poster 78: Genetic, genomic and systems biology analysis of adaptive evolution of budding yeast to the deletion of essential genes. EMBO Conference Series: Experimental approaches to evolution and ecology using yeast and other model systems. Heidelberg, Germany, 12–15 Oct, 2014.

Honors & Distinctions

• Human Frontier Science program Long-Term Fellowship (85 out of 792), 2017 

• Finalists of Kaluza prize, from ASCB (10 out of 171), 2016

• National Excellent oversea student award, China Scholarship Council, 2016

• Ray Wu Prize, Ray Wu fundation, 2016