Dr Adam West

  • Reader (Epigenetics)
  • Associate (Institute of Molecular Cell & Systems Biology)

Research interests

Grants

Grants and Awards listed are those received whilst working with the University of Glasgow.

  • Collagen IV variants and their role in intracerebral haemorrhage in the general population
    Medical Research Council
    2018 - 2021
     
  • The role of H2B ubiquitination in genome organisation.
    Biotechnology and Biological Sciences Research Council
    2012 - 2016
     
  • Engineering Zinc finger proteins for efficient gene targeting in human cells
    Tenovus Scotland
    2011 - 2013
     
  • Histone modifications at a chromatin boundary elemement
    Wellcome Trust
    2007 - 2008
     
  • The Molecular Nose
    Engineering and Physical Sciences Research Council
    2007 - 2011
     
  • Histone modifications at chromatin boundary elements.
    Wellcome Trust
    2007 - 2007
     
  • Investigating the control of CpG methylation states by a chromatin insulator
    Association for International Cancer Research
    2005 - 2008
     
  • Understanding chromatin insulator elements and their roles in gene transcription
    Medical Research Council
    2005 - 2010
     
  • The role of chromatin insulator elements in the control of gene expression
    European Commission
    2005 - 2006
     
  • Histone modifications at chromatin boundary elements
    Biotechnology and Biological Sciences Research Council
    2004 - 2007
     

Publications

List by: Type | Date

Jump to: 2018 | 2016 | 2014 | 2013 | 2012 | 2011 | 2010 | 2007 | 2006 | 2005 | 2004 | 2003 | 2002 | 2001 | 2000 | 1999 | 1998 | 1997
Number of items: 33.

2018

Garza Manero, S. et al. (2018) Maintenance of active chromatin states by Hmgn1 and Hmgn2 is required for stem cell identity. bioRxiv, (doi:10.1101/498733) (Early Online Publication)

2016

Garza-Manero, S., Sindi, A., Bailo, M., Mohan, G., Rehbini, O., Jeantet, V., West, A. and West, K. (2016) Nucleosome-binding HMGN Proteins Inhibit Stem Cell Differentiation Down the Neuronal Lineage. 2016 IMB Conference: Epigenetics in Development, Mainz, Germany, 20-22 Oct 2016.

2014

West, K. , Gourlay, E. and West, A. (2014) Genome Editing in Human Cells. Tenovus Scotland Scholarship Event, Glasgow, UK, 25 Jul 2014.

2013

Zhou, Y., Kurukuti, S., Saffrey, P., Vukovic, M., Michie, A.M. , Strogantsev, R., West, A.G. and Vetrie, D. (2013) Chromatin looping defines expression of TAL1, its flanking genes, and regulation in T-ALL. Blood, 122(26), pp. 4199-4209. (doi:10.1182/blood-2013-02-483875)

Baxter, E.W. et al. (2013) The inducible tissue-specific expression of the human IL-3/GM-CSF locus is controlled by a complex array of developmentally regulated enhancers. Journal of Immunology, 189(9), pp. 4459-4469. (doi:10.4049/jimmunol.1201915)

2012

Barkess, G. and West, A. G. (2012) Chromatin insulator elements: establishing barriers to set heterochromatin boundaries. Epigenomics, 4(1), pp. 67-80. (doi:10.2217/epi.11.112)

Hassan-Zadeh, V., Chilaka, S., Cadoret, J.-C., Ma, M., Boggetto, N., West, A. G. and Prioleau, M.-N. (2012) USF binding sequences from the HS4 insulator element impose early replication timing on a vertebrate replicator. PLoS Biology, 10(3), e1001277. (doi:10.1371/journal.pbio.1001277)

Jiwaji, M. et al. (2012) Unique reporter-based sensor platforms to monitor signalling in cells. PLoS ONE, 7(11), e50521. (doi:10.1371/journal.pone.0050521)

2011

Ma, M.K.-W., Heath, C., Hair, A. and West, A. (2011) Histone crosstalk directed by H2B ubiquitination is required for chromatin boundary integrity. PLoS Genetics, 7(7), e1002175. (doi:10.1371/journal.pgen.1002175)

2010

Dickson, J., Gowher, H., Strogantsev, R., Gaszner, M., Hair, A., Felsenfeld, G. and West, A. G. (2010) VEZF1 elements mediate protection from DNA methylation. PLoS Genetics, 6(1), e1000804. (doi:10.1371/journal.pgen.1000804)

2007

Gaszner, M., Huang, S., West, A. and Felsenfeld, G. (2007) Epigenetic regulation at the chicken β-globin locus. Blood Cells, Molecules, and Diseases, 38(2), pp. 137-138. (doi:10.1016/j.bcmd.2006.10.044)

2006

West, A.G. and van Attikum, H. (2006) Chromatin at the crossroads - meeting on signalling to chromatin epigenetics. EMBO Reports, 7(12), pp. 1206-1210. (doi:10.1038/sj.embor.7400834)

2005

Yoon, B. et al. (2005) Rasgrf1 imprinting is regulated by a CTCF-dependent methylation-sensitive enhancer blocker. Molecular and Cellular Biology, 25(24), pp. 11184-11190. (doi:10.1128/MCB.25.24.11184-11190.2005)

West, A.G. and Fraser, P. (2005) Remote control of gene transcription. Human Molecular Genetics, 14(Sup. 1), R101-R111. (doi:10.1093/hmg/ddi104)

2004

West, A.G. , Huang, S., Gaszner, M., Litt, M.D. and Felsenfeld, G. (2004) Recruitment of histione modifications by USF proteins at a vertebrate barrier element. Molecular Cell, 16(3), pp. 453-463. (doi:10.1016/j.molcel.2004.10.005)

Engel, N., West, A.G. , Felsenfeld, G. and Bartolomei, M.S. (2004) Antagonism between DNA hypermethylation and enhancer-blocking activity at the H19 DMD is uncovered by CpG mutations. Nature Genetics, 36(8), pp. 883-888. (doi:10.1038/ng1399)

Felsenfeld, G. et al. (2004) Chromatin boundaries and chromatin domains. Cold Spring Harbor Symposia on Quantitative Biology, 69(1), pp. 245-250. (doi:10.1101/sqb.2004.69.245)

2003

Yao, S., Osborne, C.S., Bharadwaj, R.R., Pasceri, P., Sukonnik, T., Pannell, D., Recillas-Targa, F., West, A.G. and Ellis, J. (2003) Retrovirus silencer blocking by the cHS4 insulator is CTCF independent. Nucleic Acids Research, 31(18), pp. 5317-5323. (doi:10.1093/nar/gkg742)

Lim, F.L., Hayes, A., West, A. , Pic-Taylor, A., Darieva, Z., Morgan, B.A., Oliver, S.G. and Sharrocks, A.D. (2003) Mcm1p-induced DNA bending regulates the formation of ternary transcription factor complexes. Molecular and Cellular Biology, 23(2), pp. 450-461. (doi:10.1128/MCB.23.2.450-461.2003)

2002

Burgess-Beusse, B., Farrell, C., Gaszner, M., Litt, M., Mutskov, V., Recillas-Targa, F., Simpson, M., West, A.G. and Felsenfeld, G. (2002) The insulation of genes from external enhancers and silencing chromatin. Proceedings of the National Academy of Sciences of the United States of America, 99(Sup. 4), pp. 16433-16437. (doi:10.1073/pnas.162342499)

Farrell, C.M., West, A.G. and Felsenfeld, G. (2002) Conserved CTCF insulator elements flank the mouse and human beta-globin loci. Molecular and Cellular Biology, 22(11), pp. 3820-3831. (doi:10.1128/MCB.22.11.3820-3831.2002)

Recillas-Targa, F., Pikaart, M.J., Burgess-Beusse, B., Bell, A.C., Litt, M.D., West, A.G. , Gaszner, M. and Felsenfeld, G. (2002) Position-effect protection and enhancer blocking by the chicken beta-globin insulator are separable activities. Proceedings of the National Academy of Sciences of the United States of America, 99(10), pp. 6883-6888. (doi:10.1073/pnas.102179399)

West, A.G. , Gaszner, M. and Felsenfeld, G. (2002) Insulators: many functions, many mechanisms. Genes and Development, 16(3), pp. 271-288. (doi:10.1101/gad.954702)

2001

Bell, A.C., West, A.G. and Felsenfeld, G. (2001) Insulators and boundaries: versatile regulatory elements in the eukaryotic genome. Science, 291(5503), pp. 447-450. (doi:10.1126/science.291.5503.447)

2000

Saitoh, N., Bell, A.C., Recillas-Targa, F., West, A.G. , Simpson, M., Pikaart, M. and Felsenfeld, G. (2000) Structural and functional conservation at the boundaries of the chicken β-globin domain. EMBO Journal, 19(10), pp. 2315-2322. (doi:10.1093/emboj/19.10.2315)

Pic, A., Lim, F.-L., Ross, S.J., Veal, E.A., Johnson, A.L., Sultan, M.R.A., West, A.G. , Johnson, L.H., Sharrocks, A.D. and Morgan, B.A. (2000) The forkhead protein Fkh2 is a component of the yeast cell cycle transcription factor SFF. EMBO Journal, 19(14), pp. 3750-3761. (doi:10.1093/emboj/19.14.3750)

1999

Bell, A.C., West, A.G. and Felsenfeld, G. (1999) The protein CTCF is required for the enhancer blocking activity of vertebrate insulators. Cell, 98(3), pp. 387-396. (doi:10.1016/S0092-8674(00)81967-4)

West, A.G. and Sharrocks, A.D. (1999) MADS-box transcription factors adopt alternative mechanisms for bending DNA. Journal of Molecular Biology, 286(5), pp. 1311-1323. (doi:10.1006/jmbi.1999.2576)

1998

Bell, A.C., Pikaart, M.J., Prioleau, M.N., Récillas-Targa, F., Saitoh, N., West, A.G. and Felsenfeld, G. (1998) Insulators and boundaries in the chicken β-globin locus. Blood Cells, Molecules, and Diseases, 24(4), pp. 464-465. (doi:10.1006/bcmd.1998.0215)

Ling, Y., West, A.G. , Roberts, E.C., Lakey, J.H. and Sharrocks, A.D. (1998) Interaction of transcription factors with serum response factor: identification of the Elk-1 binding surface. Journal of Biological Chemistry, 273(17), pp. 10506-10514. (doi:10.1074/jbc.273.17.10506)

West, A.G. , Causier, B.E., Davies, B. and Sharrocks, A.D. (1998) DNA binding and dimerisation determinants of Antirrhinum majus MADS-box transcription factors. Nucleic Acids Research, 26(23), pp. 5277-5287. (doi:10.1093/nar/26.23.5277)

1997

West, A.G. and Sharrocks, A.D. (1997) The role of DNA-bending in MADS-box transcription factor function. Biochemical Society Transactions, 25(4), S639.

West, A.G. , Shore, P. and Sharrocks, A.D. (1997) DNA binding by MADS-box transcription factors: a molecular mechanism for differential DNA bending. Molecular and Cellular Biology, 17(5), pp. 2876-2887.

This list was generated on Wed Aug 21 09:09:28 2019 BST.
Number of items: 33.

Articles

Garza Manero, S. et al. (2018) Maintenance of active chromatin states by Hmgn1 and Hmgn2 is required for stem cell identity. bioRxiv, (doi:10.1101/498733) (Early Online Publication)

Zhou, Y., Kurukuti, S., Saffrey, P., Vukovic, M., Michie, A.M. , Strogantsev, R., West, A.G. and Vetrie, D. (2013) Chromatin looping defines expression of TAL1, its flanking genes, and regulation in T-ALL. Blood, 122(26), pp. 4199-4209. (doi:10.1182/blood-2013-02-483875)

Baxter, E.W. et al. (2013) The inducible tissue-specific expression of the human IL-3/GM-CSF locus is controlled by a complex array of developmentally regulated enhancers. Journal of Immunology, 189(9), pp. 4459-4469. (doi:10.4049/jimmunol.1201915)

Barkess, G. and West, A. G. (2012) Chromatin insulator elements: establishing barriers to set heterochromatin boundaries. Epigenomics, 4(1), pp. 67-80. (doi:10.2217/epi.11.112)

Hassan-Zadeh, V., Chilaka, S., Cadoret, J.-C., Ma, M., Boggetto, N., West, A. G. and Prioleau, M.-N. (2012) USF binding sequences from the HS4 insulator element impose early replication timing on a vertebrate replicator. PLoS Biology, 10(3), e1001277. (doi:10.1371/journal.pbio.1001277)

Jiwaji, M. et al. (2012) Unique reporter-based sensor platforms to monitor signalling in cells. PLoS ONE, 7(11), e50521. (doi:10.1371/journal.pone.0050521)

Ma, M.K.-W., Heath, C., Hair, A. and West, A. (2011) Histone crosstalk directed by H2B ubiquitination is required for chromatin boundary integrity. PLoS Genetics, 7(7), e1002175. (doi:10.1371/journal.pgen.1002175)

Dickson, J., Gowher, H., Strogantsev, R., Gaszner, M., Hair, A., Felsenfeld, G. and West, A. G. (2010) VEZF1 elements mediate protection from DNA methylation. PLoS Genetics, 6(1), e1000804. (doi:10.1371/journal.pgen.1000804)

Gaszner, M., Huang, S., West, A. and Felsenfeld, G. (2007) Epigenetic regulation at the chicken β-globin locus. Blood Cells, Molecules, and Diseases, 38(2), pp. 137-138. (doi:10.1016/j.bcmd.2006.10.044)

West, A.G. and van Attikum, H. (2006) Chromatin at the crossroads - meeting on signalling to chromatin epigenetics. EMBO Reports, 7(12), pp. 1206-1210. (doi:10.1038/sj.embor.7400834)

Yoon, B. et al. (2005) Rasgrf1 imprinting is regulated by a CTCF-dependent methylation-sensitive enhancer blocker. Molecular and Cellular Biology, 25(24), pp. 11184-11190. (doi:10.1128/MCB.25.24.11184-11190.2005)

West, A.G. and Fraser, P. (2005) Remote control of gene transcription. Human Molecular Genetics, 14(Sup. 1), R101-R111. (doi:10.1093/hmg/ddi104)

West, A.G. , Huang, S., Gaszner, M., Litt, M.D. and Felsenfeld, G. (2004) Recruitment of histione modifications by USF proteins at a vertebrate barrier element. Molecular Cell, 16(3), pp. 453-463. (doi:10.1016/j.molcel.2004.10.005)

Engel, N., West, A.G. , Felsenfeld, G. and Bartolomei, M.S. (2004) Antagonism between DNA hypermethylation and enhancer-blocking activity at the H19 DMD is uncovered by CpG mutations. Nature Genetics, 36(8), pp. 883-888. (doi:10.1038/ng1399)

Felsenfeld, G. et al. (2004) Chromatin boundaries and chromatin domains. Cold Spring Harbor Symposia on Quantitative Biology, 69(1), pp. 245-250. (doi:10.1101/sqb.2004.69.245)

Yao, S., Osborne, C.S., Bharadwaj, R.R., Pasceri, P., Sukonnik, T., Pannell, D., Recillas-Targa, F., West, A.G. and Ellis, J. (2003) Retrovirus silencer blocking by the cHS4 insulator is CTCF independent. Nucleic Acids Research, 31(18), pp. 5317-5323. (doi:10.1093/nar/gkg742)

Lim, F.L., Hayes, A., West, A. , Pic-Taylor, A., Darieva, Z., Morgan, B.A., Oliver, S.G. and Sharrocks, A.D. (2003) Mcm1p-induced DNA bending regulates the formation of ternary transcription factor complexes. Molecular and Cellular Biology, 23(2), pp. 450-461. (doi:10.1128/MCB.23.2.450-461.2003)

Burgess-Beusse, B., Farrell, C., Gaszner, M., Litt, M., Mutskov, V., Recillas-Targa, F., Simpson, M., West, A.G. and Felsenfeld, G. (2002) The insulation of genes from external enhancers and silencing chromatin. Proceedings of the National Academy of Sciences of the United States of America, 99(Sup. 4), pp. 16433-16437. (doi:10.1073/pnas.162342499)

Farrell, C.M., West, A.G. and Felsenfeld, G. (2002) Conserved CTCF insulator elements flank the mouse and human beta-globin loci. Molecular and Cellular Biology, 22(11), pp. 3820-3831. (doi:10.1128/MCB.22.11.3820-3831.2002)

Recillas-Targa, F., Pikaart, M.J., Burgess-Beusse, B., Bell, A.C., Litt, M.D., West, A.G. , Gaszner, M. and Felsenfeld, G. (2002) Position-effect protection and enhancer blocking by the chicken beta-globin insulator are separable activities. Proceedings of the National Academy of Sciences of the United States of America, 99(10), pp. 6883-6888. (doi:10.1073/pnas.102179399)

West, A.G. , Gaszner, M. and Felsenfeld, G. (2002) Insulators: many functions, many mechanisms. Genes and Development, 16(3), pp. 271-288. (doi:10.1101/gad.954702)

Bell, A.C., West, A.G. and Felsenfeld, G. (2001) Insulators and boundaries: versatile regulatory elements in the eukaryotic genome. Science, 291(5503), pp. 447-450. (doi:10.1126/science.291.5503.447)

Saitoh, N., Bell, A.C., Recillas-Targa, F., West, A.G. , Simpson, M., Pikaart, M. and Felsenfeld, G. (2000) Structural and functional conservation at the boundaries of the chicken β-globin domain. EMBO Journal, 19(10), pp. 2315-2322. (doi:10.1093/emboj/19.10.2315)

Pic, A., Lim, F.-L., Ross, S.J., Veal, E.A., Johnson, A.L., Sultan, M.R.A., West, A.G. , Johnson, L.H., Sharrocks, A.D. and Morgan, B.A. (2000) The forkhead protein Fkh2 is a component of the yeast cell cycle transcription factor SFF. EMBO Journal, 19(14), pp. 3750-3761. (doi:10.1093/emboj/19.14.3750)

Bell, A.C., West, A.G. and Felsenfeld, G. (1999) The protein CTCF is required for the enhancer blocking activity of vertebrate insulators. Cell, 98(3), pp. 387-396. (doi:10.1016/S0092-8674(00)81967-4)

West, A.G. and Sharrocks, A.D. (1999) MADS-box transcription factors adopt alternative mechanisms for bending DNA. Journal of Molecular Biology, 286(5), pp. 1311-1323. (doi:10.1006/jmbi.1999.2576)

Bell, A.C., Pikaart, M.J., Prioleau, M.N., Récillas-Targa, F., Saitoh, N., West, A.G. and Felsenfeld, G. (1998) Insulators and boundaries in the chicken β-globin locus. Blood Cells, Molecules, and Diseases, 24(4), pp. 464-465. (doi:10.1006/bcmd.1998.0215)

Ling, Y., West, A.G. , Roberts, E.C., Lakey, J.H. and Sharrocks, A.D. (1998) Interaction of transcription factors with serum response factor: identification of the Elk-1 binding surface. Journal of Biological Chemistry, 273(17), pp. 10506-10514. (doi:10.1074/jbc.273.17.10506)

West, A.G. , Causier, B.E., Davies, B. and Sharrocks, A.D. (1998) DNA binding and dimerisation determinants of Antirrhinum majus MADS-box transcription factors. Nucleic Acids Research, 26(23), pp. 5277-5287. (doi:10.1093/nar/26.23.5277)

West, A.G. and Sharrocks, A.D. (1997) The role of DNA-bending in MADS-box transcription factor function. Biochemical Society Transactions, 25(4), S639.

West, A.G. , Shore, P. and Sharrocks, A.D. (1997) DNA binding by MADS-box transcription factors: a molecular mechanism for differential DNA bending. Molecular and Cellular Biology, 17(5), pp. 2876-2887.

Conference or Workshop Item

Garza-Manero, S., Sindi, A., Bailo, M., Mohan, G., Rehbini, O., Jeantet, V., West, A. and West, K. (2016) Nucleosome-binding HMGN Proteins Inhibit Stem Cell Differentiation Down the Neuronal Lineage. 2016 IMB Conference: Epigenetics in Development, Mainz, Germany, 20-22 Oct 2016.

West, K. , Gourlay, E. and West, A. (2014) Genome Editing in Human Cells. Tenovus Scotland Scholarship Event, Glasgow, UK, 25 Jul 2014.

This list was generated on Wed Aug 21 09:09:28 2019 BST.


Research in the West group

The sections below detail the project areas we pursue in the West group. In general, we are interested in how transcription factors bound at gene regulatory elements can influence epigenetic chromatin states to regulate gene transcription. We seek a deeper understanding of chromosomal organisation by enhancer and insulator elements. We also translate this understanding to solving long standing problems in the biotechnology and genetic therapy sectors.

Inevitably, enabling technologies play a key part in our research. We have therefore invested considerable effort in developing a powerful gene reporter system, protein labelling in living cells and exciting genome / epigenome editing approaches using CRISPR and TALE technologies. These will be fundamental to our work in the next few years.

Chromatin domains and their boundaries


Evidence from chromatin profiling, chromosomal interaction mapping and functional assays all support the hypothesis that genome organization and long range gene regulation in metazoa involves the partitioning of genomes into distinct chromatin states. There is also strong evidence that the transcriptional regulation of genes and gene clusters within these chromatin domains can be maintained independently of their surroundings through the establishment of chromatin boundaries. These boundaries sometimes vary in position as a result of a balance between countervailing chromatin opening and condensing processes. Alternatively, chromatin boundaries of fixed position can be established by specific DNA sequence elements and their associated binding proteins. Such elements, collectively called insulators, possess a common ability to protect genes from inappropriate signals emanating from their surrounding environment.


Lessons from studying a model chromatin boundary

The chicken β-globin gene locus is a model example of chromatin domain organisation. Upon their expression, the β-globin genes are clustered within a thirty kilobase domain of open chromatin flanked by condensed chromatin that is repressive to transcription. The 5´ boundary of the globin domain is marked by the remarkable HS4 insulator element, which harbours enhancer blocking and heterochromatin barrier activities. The protein CTCF directs the enhancer blocking of HS4 and thousands of insulators throughout vertebrate genomes. CTCF interacts with cohesin proteins and forms chromosomal loop interactions that are widely considered to contribute to genome organization. Only a small subset of CTCF sites are proximal to chromatin boundary features, so it remains likely that other insulator proteins, with heterochromatin barrier-specific functions perhaps, function to partition chromosomal domains.

HS4 became useful again, as we found that its heterochromatin barrier activity did not require the CTCF site. Instead, HS4 requires the activities of the USF1/2 and VEZF1 transcription factors, which direct different mechanisms to counter the propagation of chromatin silencing.


Mechanisms of chromatin boundary formation

The role of H2B ubiquitination in chromatin boundary formation

The USF transcription factors act to recruit several histone modifying enzymes to HS4, including P300, PRMT1 and SET1, that result in the acetylation of H3, H4 and H2A.Z and the methylation of H3K4 and H4R3. Recently, we also found that USF1 mediates H2B mono-ubiquitination (H2Bub1) at insulators in chicken cells. Our experiments revealed that H2Bub1 is required for the histone modification signature at chromatin boundary elements, consistent with this mark acting at the head of a histone modification cascade. Collectively, these so-called “active” histone modifications at boundary elements act as a chain terminator to the propagation of histone modifications associated with heterochromatin assembly. Depletion of H2Bub1 allows the spreading of heterochromatin beyond its normal limits, resulting in the progressive silencing of nearby gene transcription. We are currently studying this process across the human genome.

The many roles of the VEZF1 transcription factor

Our earlier studies of the HS4 insulator found that multiple sites for the transcription factor VEZF1 were required for heterochromatin barrier activity. These sites were all associated with HS4’s resistance to DNA methylation. We also found VEZF1 sites abrogated DNA methylation at the Hprt CpG island promoter. In pursuing these interesting results, we have new data that shows VEZF1 has much broader gene regulatory roles than first expected. This is now a major focus of the group.


Identification of novel chromatin opening elements that facilitate stable gene expression

The understanding of mammalian chromatin boundary elements has been limited by the lack of a gene reporter assay that can be scaled up to assay new candidate elements and allow for direct comparisons between assays in controlled chromosomal locations. We therefore invested considerable effort in developing such an assay system. We have teamed up with our collaborators at UCB Celltech to identify and validate new elements that enable stable transgene expression. Recombinant genes tend to be become silenced when integrated in the genome of host cells as most of the genome is repressive to transcription at any given time. This represents a major bottleneck to the manufacturers of biopharmaceuticals, who currently invest extensive time and effort to identify mammalian cell lines that express recombinant genes at a high level for long periods. Our combined skills in identifying candidate chromatin opening elements, the new assay system and expertise in recombinant protein production are being used to reduce the effort required to develop highly productive cell lines, ultimately bringing down the cost and developmental timelines for the latest targeted therapies.


Genome and epigenome modification

Gene modification strategies

Recent advances in synthetic biology allow molecular biologists to make alterations to the genome of pretty much any species. The new approaches use DNA endonucleases to cleave a chosen sequence, which becomes mutated by error-prone DNA repair mechanism in host cells. This is a rapid and convenient way to mutate genes for functional studies. The West group has established both multiplex CRISPR/Cas9 and optimised TALEN platforms, each suited for different applications. Despite the ease and power of these new technologies for gene disruption, making accurate genetic modifications, particularly gene insertions, is challenging. The group are developing new strategies to address this challenge, which should impact the genetic therapy and biotechnology fields.

Epigenetic modification

Transcription Activator Like Effector (TALE) proteins are transcription factors with a unique modular DNA-recognition mechanism. TALE proteins can be readily engineered to bind to any DNA sequence of choice. Likewise, dCas9, a deactivated version of the CRISPR enzyme, can be used as an RNA-guided DNA-binding protein. The fusion of effector domains onto TALE or dCas9 proteins creates new transcription factors that can alter gene expression programmes or interrogate candidate gene regulatory elements. The West group is using both platforms to activate, repress or label genetic elements to study gene regulation. Epigenetic engineering not only complements genome modification, but is also reversible and offers insight into the specific contributions of histone and DNA modifications.