Dr Bin Hu

Biography

01/2020-                Lecturer in Medical Science, School of Medicine, Medical Sciences & Nutrition; University of Aberdeen, UK

01/2015-01/2020    Research Fellow (Principle Investigator), Department of Molecular Biology and Biotechnology, University of Sheffield,UK

11/2008-01/2015    Postdoctoral Research Associate, Department of Biochemistry, University of Oxford, UK

02/2006-10/2008    Postdoctoral Research Associate, Department of Biochemistry, King’s College London, UK

02/2002-11/2005    Ph D in Molecular Genetics, Department of Biochemistry, King’s College London, UK 

Research Overview

My interests focused on regulation and structure basis of cohesin function, which is fundamental to DNA condensation, DNA damage repair and gene transcription. Following DNA replication during cell division, sister chromatids (duplicated chromosomes) are held together until the end of metaphase to prevent premature segregation, and to ensure genetic information is transmitted equally into two daughter cells. A multi-subunit protein complex called cohesin is the key player in holding sister chromatids together in a process termed sister chromatin cohesion (SCC). Besides its canonical function of SCC, cohesin also participates in organising high-ordered chromosomal structure, in repairing DNA double-strand breaks and in regulating gene transcription. Mutations in cohesin subunits and its regulators give rise to several types of inherited developmental disorders, such as Cornelia de Lange syndrome (CdLS) and Roberts syndrome. Cohesin is highly conserved across the eukaryote and investigation of how cohesin performs its various functions at a molecular level is fundamental in the field of chromosome biology and gene transcription, which is crucial to develop a wider understanding of how eukaryotic cells work.  The knowledge we gain on fundamental molecular mechanisms will contribute to future understanding of the causes of such disorders, and in long term provide a solid foundation for their prevention and therapy.

My lab also works on DNA recombination during meiosis, a critical process responsible for genetic diversity. All sexually reproducing organisms produce haploid gametes that are characterised as germ cells through meiosis. These gametes are created by halving the number of chromosomes in order to ensure that the offspring will be full diploid upon fertilisation. A key feature of the meiotic division is that the four gametes derived from one mother cell are genetically distinct, which permits subsequent fertilisation to introduce genetic variation into the next generation. Continuing this process through generations will increase genetic variability within populations, potentially conferring to advantage and increasing fitness for survival in unpredictable environments. This feat is only achievable because the homologous maternal and paternal chromosomes are fragmented and re-assembled in meiosis so that the chromosomes in the daughter cells are collages of grandparental genetic material. This process is commenced with programmed DNA double-strand breaks (DSBs) created by Spo11 - a topoisomerase-like protein which introduces around 200 DSBs along the yeast genome. Those DSBs are repaired by a conserved mechanism called homologous recombination, which leads to the exchange of genetic materials between homologue chromosomes. In this process, the DSBs are first resected to expose 3’ single-stranded DNA (ssDNA) overhangs, facilitating the following Dmc1/Rad51 mediated strand invasion. There are two key factors required for DNA resection: Sae2-associated MRX complex and Exo1. The resection starts with the MRX complex by nicking the DNA with its endonuclease activity followed by 3’ to 5’ direction resection with its exonuclease activity. This results in the removal of covalently bound Spo11 and formation of a short 3’-ssDNA tail. To produce a long tract of 3’ ssDNA, the DNA resection is taken over by Exo1, which further resects DNA from 5’ to 3’ direction.  My lab is addressing how is the resection is regulated during meiosis. The answer to this question will provide novel insight into the regulation of resection and homologous recombination, which is fundamental to create genetic diversity in nature.  

Funding and Grants