AnneResearch summary

Our lab is interested in how genetic material is packaged in eukaryotes and the implications this has for biological processes. Within each cell of our body, we have nearly four metres of DNA distributed over 46 chromosomes which is sequestered in a nucleus of only 1000 m3. Chromatin must, therefore, fulfil two conflicting roles: structure DNA so that genomic instability is minimised, but at the same time remain accessible to factors involved in transcription, replication and repair. In studying these contrary roles, our investigations span two length scales, namely the assembly of individual nucleosomes to form the 10 nm fibre and the mechanics of higher-order chromatin domains. To do this we utilise both in vitro biochemical approaches and advanced live-cell imaging.

 

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A histone matchmaker

A new preprint detailing work led by Alonso Pardal defining a pathway specific for the import and dimerisation of monomeric histones.

 

 

 

 

Alonso J. Pardal, Andrew J. Bowman.
Nuclear import and chaperoning of monomeric histones H3 and H4 is mediated by Imp5, NASP and the HAT1 complex

bioRxiv 2021.10.19.464968.
[Link]

 

Cradle to grave

Alonso and Fil summarise the current literature on histone chaperoning from "ribosome to nucleosome".

 

 

 

 

Pardal A.J., Fernandes-Duarte F., Bowman A.J. (2019)
The histone chaperoning pathway: from ribosome to nucleosome

Essays Biochem. 63(1):29-43. Review.
doi:org/10.1042/EBC20180055
[Link]

 

RAPIDPulsing histones

Mike and Andrew develop a real-time pulse chase strategy called 'RAPID-release' to probe the histone chaperoning pathway & propose a pathway for the import of monomeric histones.

 

 

 

 

 

 

Apta-Smith M.J., Hernandez-Fernaud J.R., Bowman A.J. (2018)
Evidence for the nuclear import of histones H3.1 and H4 as monomers.

EMBO J. doi:10.15252/embj.201798714.
doi:org/10.15252/embj.201798714
[link]

 

>> see all publications here

 

AndrewAndrew Bowman | PI

Originally from the South East of England, I read biochemistry at Leicester before moving to the University of Dundee to do my PhD under Tom Owen-Hughes. My PhD was focused predominantly on using pulsed EPR to probe the structure of the H3-H4 tetramer complex in solution. After my PhD I continued in the chromatin field carrying out a postdoc at the LMU in Munich in the lab of Andreas Ladurner. There I investigated the role of TPR proteins in histone chaperoning, revealing a novel histone peptide binding module in the protein NASP (Bowman et al., 2016), and discovered a minimal two-chaperone system for the efficient folding of an H3-H4 dimer in vitro (Bowman et al., 2017).

Following my postdoc I took up a position as an Independent Research Fellow at the University of Warwick as part of the Warwick-Wellcome Quantitative Biomedicine Program. During this time I became interested in using a broader range of tools to study the dynamics of the histone chaperoning network. Combining a novel synthetic pulse-labelling technique (RAPID-release) with microscopy and more traditional biochemical tools, we proposed that histones H3 & H4 are rapidly imported into the nucleus as monomers, not as dimeric units, and that a stable nuclear pool of monomeric H3 exists bound to NASP (Apta-Smith et al., 2018).

Currently I am a Sir Henry Dale Fellow.

2018 - Present: Sir Henry Dale Fellow, Warwick
2015 - 2018: Independent Research Fellow, Warwick
2013-2015: Marie Curie Fellow, Munich
2011-2013: EMBO fellow, Munich
2010-2011: Research associate, Dundee
2006-2010: PhD student, Dundee
2002-2006: BSc Biochemistry, Leicester

 

lab members & projects

DanielAlonso Pardal | postdoc | funded by Wellcome Trust

I studied Pharmacy and Pharmacology and a Masters in Plant Biotechnology in the University of Salamanca (Spain). Following that, I moved to the University of Warwick to do his PhD with Vardis Ntoukakis working on the role of chromatin remodelling complexes in gene reprogramming during microbial infection.

Currently I am combining proximity labelling with the RAPID-release approach to study the kinetics of histone-chaperone interactions during their journey from ribosome to chromosome.

 

SeharSehar Sajid| Postdoctoral Fellow | 2019-2020

I worked on a joint project with Prof. Victor Zammit investigating the cellular targeting of ACC2 in human cells using confocal microscopy

I am currently in Pakistan

MikeMike Apta-Smith| Postdoctoral Fellow | 2016-2017

I studied histone deposition and helped develop the RAPID-release approach.

I moved on to a postdoc position in Colin Taylor's lab, Cambridge.







FilFilipe Fernandes Duarte | PhD student | funded by MRC

I am originally from Portugal, having studied biochemistry & genetics at the University of Lancaster before joining the MRC-DTP graduate program. After a mini project in the lab during my MSc year, I decided to return to undertake my full PhD.

I am currently persuing a career in consulting in the medical/biotech field



My project involved combining tether-and-release approaches to observe the dynamics of replication domains in single, living cells by pulse-labelling chromatin with fluorescent histones. .

oliviaOlivia Bradley| Undergraduate student Intergrated Sciences MSci | 2021

I studied the role of UBR7 in histone metabolism

I am now continuing my studies on the Integrated Sciences MSci program.

sarahSarah Pritchett| Rotation student Midlands Integrative Biosciences Training Programme | 2021

I studied the role of Importin proteins in the histone deposition pathway

I am now undertaking my second miniproject and then my PhD with John Schwabe at Leicester.

nicoleNicole McFadzean| Rotation student Midlands Integrative Biosciences Training Programme | 2019

I further developed the spy-tag approach for investigating histone multimerisation during nucleosome assembly

I am now undertaking my PhD at the University of Birmingham.

MarcoMarco| ERASMUS student | 2018

I used the spy-tag for studying histone partitioning during replication

I moved on to a second studentship in Finland

nicoleNicole Matthews| MRC-DTP IBR Summer Student | 2018

I studied the incorporation of histones into chromatin using the RAPID-release approach.

I am now a PhD student at the ICR in London

ElodieElodie Debray| Undergraduate project student | 2016

I studied the role of histone acetylation in nucleosome assembly.

I moved back to the University of Angers in France to finish my studies.

 

Sir Henry Dale Fellowship | Wellcome Trust/Royal Society
Probing the chromatin assembly pathway.
2018-2023

 

Warwick Quantitative Biomedicine Programme Fellowship | Wellcome Trust / University of Warwick
Live-cell imagine approaches in studying chromatin assembly.
2015-2018

 

>> British Science Festival - University of Warwick, Sept 2019

 

BSF Above | Fil joined the Warwick QBP team to deliver a practical in DNA extraction at the British Science Festival.


>> Cafe Scientifique - Leamington Spa, April 2019

 

Above | Fil presented his Ph.D. project in a Cafe Scientifique talk in Leamington Spa.

 


>> U3A talk - Warwick, 25th Apr 2018

 

Andrew gave a talk to the Warwick division of the University of the Third Age on 'Gene Editing', with practical demonstrations on how to decode DNA, therapeutic strategies to cure sickle cell anaemia, and precision genome engineering using CRISPR-Cas9!

U3A

 


>> 'Let me take a cell-fie', 23rd March 2018

Warwick QBP Cell Biology Image Competition: Bowman lab submits two entries.

 

Below | Batman appearing mysteriously in SDS-PAGE gel - unfortunately he didn't make it to the final

Batman

 


Nuclear Wrap

Above | The shortlisted image of ACC2 perinuclear localisation in cancer cells.


 

>> Pecha Kucha - Coventry, 29th June 2017

pecha

With support from the Warwick Quantitative Biology Program we organised a Pecha Kucha evening at The Tin in Coventry. Speakers from Warwick Medical School gave 20x20 presentations (20 slides, 20 seconds each) on their research, with guest speakers from the University of Birmingham (Ferenc Mueller), Tel Aviv University (Oded Rechavi) and The University of Oxford (Jane Mellor).

 

 

 

The Dicky Bows

Interested in chromatin? Join The Dicky Bows (neck tie optional).

 

Fellowships


We are always interested in hearing from motivated individuals who have an interest in using interdisciplinary methods to investigate chromatin structure and function. If you are interested in joining the Bowman lab, contact Andrew Bowman with your CV and a brief overview of your research interests to discuss funding opportunities.

 

The University of Warwick has a number of doctoral training partnerships, including the MRC-DTP [link], the MIBTP [link] & the Warwick CDT for Analytical Science, [link] in addition to the Chancellor's International Scholarship [link], the Chancellor's EU Scholarship [link] and others (you can check the University's scholarship page [here].

Selected Publications

 

Pardal A.J., Fernandes-Duarte F., Bowman A.J. (2019) The histone chaperoning pathway: from ribosome to nucleosome.
Essays Biochem. 63(1):29-43. (Review)

 

Apta-Smith M.J., Hernandez-Fernaud J.R., Bowman A.J. (2018) Evidence for the nuclear import of histones H3.1 and H4 as monomers.
EMBO J. doi:10.15252/embj.201798714.

 

Bowman, A., Koide, A., Goodman, J.S., Colling, M.E., Zinne, D., Koide, S., and Ladurner, A.G. (2017). sNASP and ASF1A function through both competitive and compatible modes of histone binding.
Nucleic Acids Res 45, 643-656.

 

Bowman, A., Lercher, L., Singh, H.R., Zinne, D., Timinszky, G., Carlomagno, T., and Ladurner, A.G. (2016). The histone chaperone sNASP binds a conserved peptide motif within the globular core of histone H3 through its TPR repeats.
Nucleic Acids Res 44, 3105-3117.