Hansong Ma
Group leaderResearch summary
Mitochondrial DNA transmission and maintenance
In addition to the nuclear genome, all animals have another genome packed inside the mitochondrion called mtDNA. This maternally inherited genome encodes important proteins for energy production. During development and ageing as mtDNA continues to replicate and turnover, mutations can occur to some of the copies. The subsequent prevalence of these mutants, which determines the progression and inheritance of the clinical abnormalities of mitochondrial disorders, depends on how they compete with the co-existing wild-type genomes for transmission. To date, over 50 mtDNA-linked disorders have been described in humans.
We are interested in understanding the molecular mechanisms that govern mtDNA heteroplasmy transmission during development and ageing. In particular, we want to know why a mutant mitochondrial genome increases in abundance to cause diseases in some cases while in others, it is eliminated. By creating fruit flies carrying both functional and pathogenic mitochondrial genomes, we perform systematic and detailed studies to identify nuclear factors and mtDNA sequence polymorphisms that bias the transmission of one genome over the other to impact the progression and inheritance of mtDNA-linked disorders.
Diagram of mitochondrial DNA in the fruit fly, a multi-copy genome that shows complex transmission patterns during developing and aging, and between generations.
We are also interested in understanding how repair mechanisms maintain mtDNA integrity during development, how maternal inheritance of mtDNA is guaranteed and how complex mito-nuclear interactions modulate the pathogenic expression of mtDNA mutations. These studies provide insights into genome evolution, ageing and human diseases.
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Selected publications
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Klucnika A, Ma H (2019) Mapping and editing animal mitochondrial genomes: can we overcome the challenges? Phil Trans Roy Soc B. 375 (1790): DOI: 10.1098/rstb.2019.0187.
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Chiang C-Y, McCartney E, O’Farrell PH & Ma H (2019) A genome-wide screen reveals that reducing mitochondrial DNA polymerase can promote elimination of deleterious mitochondrial mutations. Current Biology 29:1-7. DOI: 10.1016/j.cub.2019.10.060.
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Klucnika A, Ma H (2019) A battle for transmission: the cooperative and selfish animal mitochondrial genomes. Open Biology 9. DOI: 10.1098/rsob.180267.
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Ma H, O’Farrell PH (2016) Selfish drive can trump function when animal mitochondrial genomes compete. Nat Genet 48(7):798-802.
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Ma H, O’Farrell PH (2015) Selections that isolate recombinant mitochondrial genomes in animals. Elife 4:e07247.
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Ma H, Xu H, O’Farrell PH (2014) Transmission of mitochondrial mutations and action of purifying selection in Drosophila melanogaster. Nat Genet 46(4):393-397.
Biography
Dr Hansong Ma PhD, Group Leader, Wellcome Sir Henry Dale Fellow, Member of the University Department of Genetics.
Hansong studied the host-pathogen interaction for her DPhil at the University of Birmingham under the supervision of Prof Robin May. She then joined Prof Patrick O’Farrell’s laboratory as a Human Frontier postdoctoral fellow at the University of California San Francisco to explore mitochondrial DNA (mtDNA) transmission in Drosophila. In 2017, she started her group as Wellcome Sir Henry Dale Fellow at the Gurdon Institute to continue her work in heteroplasmy transmission. She also obtained an ERC Starting Grant in 2018 to study mtDNA recombination.
Hansong is an expert in the field of mitochondrial genetics. Among her ground-breaking research advances, Hansong showed that deleterious mitochondrial DNA (mtDNA) mutations are selectively eliminated by purifying selection, but certain sequence polymorphisms can grant pathogenic mitochondrial genomes selfish transmission advantages so that they outcompete functional genomes and impair health. Moreover, Hansong has demonstrated that homologous recombination occurs in animal mitochondria and capitalised on this to develop the first system to isolate recombinant mtDNA, providing a means to genetically engineer animal mtDNA.
By illuminating the mechanisms underlying mtDNA competition and maintenance, her research will lead to interventions that could alleviate or even prevent mitochondrial diseases and age-related decline in mtDNA quality. Her contribution to the mitochondrial genetics field and the great potential of her future research was recently recognised by the Leverhulme Trust, which granted her the Philip Leverhulme Prize in 2020. She is also an EMBO Young Investigator (2021-2024).
Notable achievements and honours
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2021-2024EMBO Young Investigator
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2020Philip Leverhulme Prize in Biological Sciences
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2017Wellcome Sir Henry Dale Fellow
Research group
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Dr Chieh-Yin (Ason) Chiang
Research Associate
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Dr Nuria Cortes Silva
Research Associate
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Dr Ivy Di
Research Assistant
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Beitong Gao
PhD Student
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Andy Yu Zhi Li
PhD Student
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Matthew McCormack
PhD Student
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Sumaera Rathore
PhD Student
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Ziming Wang
PhD Student
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Xieze Xu
MPhil Student