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News at the BCGB

MRes in Functional Genome Biology starting in September 2022

BCGB and The Institute of Cancer and Genomic Sciences are launching a new MRes in functional genome biology course in September 2022. Genome biology is the biological science of the 21st century and has the potential to transform medicine. It is powerfully informative about how DNA and genomes are organised and controlled. An understanding of its core principles and how it responds to stresses and interventions is a requirement for future research leaders.

This programme places you at the centre of world-leading expertise to provide a unique training experience, offering cutting-edge taught and research training in all aspects of genome biology. As a research Masters degree, it prepares you for the next stage in a research career. Its delivery focuses on substantial hands-on, real world training to give you the employability skills you will need for PhD and industry positions.

Apply here to join this course

Post-lockdown report from BCGB (September 2021)

The last year and a half has been difficult for everyone, and especially hard for research labs that had to endure complete laboratory shut-downs for many months and severely restricted access to labs and offices at other times. However, that does not mean we have been unproductive. While working from home many of our members used this time to publish research articles based on data that they had already accumulated before the COVID19 pandemic struck. This made a substantial contribution to the University of Birmingham’s REF submission with many of these outputs ranked internally as 4 star publications. It is impossible to list them all here but here are just some of the highlights:

In the area of Epigenetics and Gene Regulation, the Bonifer/Cockerill group had a string of papers covering both Cancer Genomics and Molecular Immunology. Continuing on the theme of gene regulation and epigenetics in acute myeloid leukaemia (AML), which produced a Nature Genetics paper on gene regulatory networks in AML in 2019, Potluri et al showed in Cell Reports in 2021 that the transcription factor WT1 mediates oncogenic signalling to control AML growth. In a study in 2020, Chin et showed in Experimental Hematology that RUNX1/ETO and mutant KIT collaborate to re-programme  transcription in AML with t(8;21) translocations, while Nafria et al showed in 2020 in Cell Reports that RUNX1-ETO interferes with normal RUNX1 binding to block early myeloid cell development. Kellaway et al showed in Haematologica in 2021 that RUNX1-EVI1 disrupts the gene regulatory networks controlling differentiation in AML with t(3;21) translocations, and also showed in Life Science Alliance in 2021 that different mutant RUNX1 oncoproteins re-program different differentiation pathways. Daniel Coleman’s contribution to the Nature Genetics paper was also acknowledged when he was awarded a Goldman Fellowship in 2021 by Leukaemia UK.

On the T cell front, Bevington et al published 3 landmark papers on gene regulation and epigenetics during T cell differentiation. One study in EMBO in 2020 revealed that T cell differentiation is actually initiated by IL-2 and IL-7 when naïve T cells are activated the first time, making cells receptive to differentiation factors which are only expressed much later. A collaboration with David Wraith in Cell Reports in 2020 defined the molecular basis of a peptide de-sensitisation therapy used in Multiple Sclerosis patients that renders auto-immune cells tolerant. A collaboration with David Withers in Frontiers in Immunology in 2021 defined the molecular basis of immunological memory by using antigen-specific T cells to show that memory T cells acquire stable epigenetic priming at immune response genes in response to antigen.    

Also in the field of gene regulation in leukaemia, the Stankovic lab made major advances in the field of chronic lymphocytic leukemia (CLL). Kwok et published in Blood in 2020 the molecular basis for spontaneous regression in CLL. Marwon Kwok’s contribution was recognised with the Hamblin prize for the best CLL paper in 2020, the Trainee prize from the Royal College of Pathologists, and a 3 year fellowship from CRUK to study at Harvard.

With a change of subject now to zebrafish, the Mueller lab showed in Developmental Cell in 2021 that the germ plasm determining factor Tdrd7 controls the development of the germ plasm from primordial germ cells by programming transcriptional networks that govern cell fate decisions between germ cells and somatic cells. In a second study in Nature Communications in 2020, Nepal et al showed that many gene promoters in zebrafish, and also humans, utilise 2 distinct classes of transcription initiation sequences within individual promoters that are differentially regulated during the transition from maternal to zygotic gene expression during embryogenesis. Also in zebrafish, Rui Monteiro showed in Communications Biology that a conserved enhancer controlling the GATA2 gene is required for development of both blood cells and endothelial cells.

In one of 2 significant publications involving insect models, the Badenhorst group used drosophila as a model of inflammation to publish a study in Life Science Alliance in 2020 to show that oxidised dietary unsaturated fatty acids activate pro-inflammatory signalling pathways linked to JNK that phosphorylate the transcription factor FOXO, a transducer of insulin signalling, and render it unresponsive to insulin signalling.

In a study looking at honey bees, a study from the Soller group in Scientific Reports in 2021 revealed that the devastating effects of widely used neonicotinoid insecticides can be linked to changes in gene expression and increased susceptibility to bacterial infections.

A study of bacterial gene transcription published by the Grainger lab in Nature Microbiology in 2021 identified an abundant class of symmetrical bidirectional promoters that regulate divergent genes in E.Coli and in Archaea.

In the area of DNA replication and repair, the Stewart lab showed in Nature Communications in 2020 that the balance between early and late DNA replication is controlled by DONSON and FANCM associating with different replication origins. On a similar theme, the Akerman lab showed in Nature Communications in 2020 that different cell types share a core of replication origins that are defined as G-rich origins. In another study in The Journal of Clinical Investigation from the Stewart and Higgs labs in 2020, they showed that germline mutations in the RBBP8 gene, a regulator of homologous recombination during DNA repair, are responsible for a subset of early onset breast cancers. A study from the Saponaro lab showed in Cell Reports in 2021 that persistent transcription during DNA replication leads to a delay of replication timing of these transcribed regions. A team effort from several groups in BCGB, led by Paloma Garcia and published in EMBO Reports in 2021, showed that MYBL2 functions to suppress replication stress and genome instability in stem cells. A study from the Petermann and Morris labs in Nature Communications in 2020 identified the priming polymerase PrimPol as factor that leaves gaps in replicated DNA where replication is stalled by bulky DNA adducts, which require post-replication repair via DNA resection by RAD51 and homologous recombination.

Finally on the COVID19 front, Pawel Grzechnik joined a team of UoB chemists and virologists to develop molecules that form supramolecular barrel structures capable of blocking viral replication. The characterisation of these novel therapeutics was published in 2021 in Angew Chem Int Ed Engl.

Promotions and awards for BCGB members in 2020 and 2021

Jo Parish and Andrew Beggs were promoted to Professor. 
Eva Petermann and Aga Gambus were promoted to Reader.
Dr Martin Higgs, Dr Marco Saponaro, and Dr Ildem Akerman were promoted to Senior Lecturer.

Well done to all. 

 

 

 

 

 

 

Jo Parish

 

 

 

 

Andrew Beggs

 

 

 

 

Eva Petermann

 

 

 

 

Aga Gambus

 

 

 

 

Martin Higgs

 

 

 

 

 

Dr Marco Saponaro

 

 

 

 

Dr Ildem Akerman

Previous news 

In 2019, Professor Jo Morris published a paper in Nature describing a novel mechanism regulating the structure of the BRCA1 protein and how mutations in breast cancer prevent the BRCA1 protein from adopting the correct structure. BRCA1 normally protects the genome from DNA damage and this function is controlled by an isomerase that puts a bend in the BRCA1 protein. The Morris laboratory showed that some mutations occur in the isomerisation site and bypass this mode of regulation, and block normal BRCA1 function.