Amanda Fisher

Professor Amanda Fisher joins us from Imperial College London where she led the Institute of Clinical Sciences and was Director of the Medical Research Council (MRC) London Institute of Medical Sciences (LMS) at the Hammersmith Hospital campus for more than 10 years. She is a Cell and Molecular Biologist with a long-standing interest in understanding the establishment and maintenance of cell fate. As a post-doc at the NIH she obtained the first biologically active isolates of HIV early on in the AIDS pandemic. She returned to the UK to start her own laboratory at the MRC Clinical Sciences Centre, the forerunner of the LMS, focusing initially on lymphocyte development, and subsequently broadening out to other classical cell fate models, including embryonic stem cells.  Her more recent research investigates the transmission of epigenetic information through mitosis and the effect of the maternal environment on epigenetic gene regulation.  Further information on Mandy’s research can be found here: Epigenetic Memory Research Group | Amanda Fisher | LMS (mrc.ac.uk).  In addition to her major research contributions, Professor Fisher has pioneered highly impactful schemes to support the careers of scientists and to promote public understanding of science.  A standout example is the Suffrage Science Award, celebrating and inspiring the careers of women in science (Suffrage Science award - Wikipedia)

 

In recognition of her many achievements, Mandy was elected a member of EMBO in 2001 and awarded the EMBO Gold Medal in 2002. She was elected a Fellow of the Academy of Medical Sciences (FMedSci) in 2003, and a Fellow of the Royal Society in 2014. She was appointed a DBE (Dame) in the 2017 New Year Honours for services to medical research and the public understanding of science.

 

Cells within a multicellular organism contain the same DNA but have different functions. This ‘specialisation’ is achieved through differential gene expression, a process underpinned by the action of transcription factors and epigenetic regulators such as non-coding RNAs, modified histones and DNA methylation. 

To ensure that cell identity is maintained as cells divide, epigenetic information must be maintained and transmitted through the cell cycle. This is particularly important during DNA synthesis (in S-phase) and when chromosomes segregate in mitosis (M-phase). We study how epigenetic information is transmitted through cell division and across generations. To do this we develop convergent molecular, proteomic and imaging approaches to examine the repertoire of factors that remain associated with mitotic chromosomes. These factors are critical for maintaining the structure of mitotic chromosomes and have also been implicated in ‘bookmarking’ of genomes to ensure that cell identity is correctly reinstated in daughter cells following cell division.

Our long-term goal is to uncover the molecular interplay between DNA-binding proteins and chromatin states that determine heritable gene silencing and inducible activation. We use a variety of genetic and cell biology tools to discover epigenetic mechanisms that regulate gene expression during development and are altered in disease settings.

Djeghloul D, Patel B, Kramer H, et al., 2020, Identifying proteins bound to native mitotic ESC chromosomes reveals chromatin repressors are important for compaction, Nature Communications, Vol:11, ISSN:2041-1723, Pages:1-15

Bruno L, Ramlall V, Studer RA, et al., 2019, Selective deployment of transcription factor paralogs with submaximal strength facilitates gene regulation in the immune system, Nature Immunology, Vol:20, ISSN:1529-2908, Pages:1372-1380

Ferreirós-Vidal I, Carroll T, Zhang T, et al., 2019, Feedforward regulation of Myc coordinates lineage-specific with housekeeping gene expression during B cell progenitor cell differentiation, PLOS Biology, Vol:17, ISSN:1544-9173

Merkenschlager M, Cuartero S, Weiss F, et al., 2018, Control of inducible gene expression links cohesin to hematopoietic progenitor self-renewal and differentiation, Nature Immunology, Vol:19, ISSN:1529-2908, Pages:932-941

Van de Pette M, Abbas A, Feytout A, et al., 2017, Visualizing changes in Cdkn1c expression links early life adversity to imprint mis-regulation in adults, Cell Reports, Vol:31, ISSN:2211-1247, Pages:1090-1099

Cantone I, Dharmalingam G, Chan YW, et al., 2017, Allele-specific analysis of cell fusion-mediated pluripotent reprograming reveals distinct and predictive susceptibilities of human X-linked genes to reactivation, Genome Biology, Vol:18, ISSN:1474-760X

Fisher AG, 2016, Ordered chromatin changes and human X chromosome reactivation by cell fusion-mediated pluripotent reprogramming, Nature Communications, Vol:7, ISSN:2041-1723

Gupta P, Lavagnolli T, Mira-Bontenbal H, et al., 2015, Cohesin's role in pluripotency and reprogramming., Cell Cycle, Vol:15, ISSN:1551-4005, Pages:324-330