Dr Adam Cook

Postdoctoral Fellow
Medicine, Central Clinical School
Centenary Institute of Cancer Medicine & Cell Biology

Telephone +61 2 9565 6245
Fax +61 2 9565 6101

Map

Biographical details

I completed a Bachelor of Medical Science (Hons) at the University of Sydney in 2002 and subsequently a PhD under the supervision of Dr Christopher Jolly at the Centenary Institute (Sydney) where I investigated the role of DNA repair proteins in antibody gene class switching and mutation in B lymphocytes.A recipient of La Ligue Contre le Cancer (French Cancer Council) and NHMRC CJ Martin Postdoctoral Fellowships, I joined the lab of Dr Geneviève Almouzni at the Institut Curie in Paris in where I turned my attention to the regulation of chromatin dynamics in maintaining genome function and stability. I returned to Australia in 2011 and joined the lab of Prof. David Tremethick at the John Curtin School of Medical Research, Australian National University (Canberra), to complete a second postdoc. In 2012 I was awarded a University of Sydney Postdoctoral Research Fellowship which allowed me to return to the University and Centenary Institute in 2013 where I am continuing my research within the Immune Imaging Laboratory.

Research interests

I am broadly interested in understanding how the packaging of DNA with histone proteins into chromatin is properly regulated to ensure genome integrity and function. My specific area of interest is the role of histone chaperone proteins in coordinating histone dynamics and metabolism and how failure to regulate their activity can lead to genome instability and cancer.

I have available several options for postgraduate research projects, including:

1) Evaluating histone regulatory proteins as novel prognostic and diagnostic cancer markers

The eukaryotic genome is packaged with histone proteins into chromatin. Since all transactions with DNA occur in the context of chromatin, histones play an intimate role in regulating genome function and integrity. Failure to properly handle histones at any point throughout their cellular ‘life’ can therefore perturb DNA replication, cause genome instability and potentially lead to cancer.

At all points in their cellular life during which they are not a part of chromatin, histones are escorted by a network of proteins known as histone chaperones (http://pubmed.org/23288364; http://pubmed.org/20444609). Dr Cook and colleagues recently revealed a novel role for one histone chaperone in regulating the supply of histones (http://pubmed.org/22195965), in particular during DNA replication stress, a hallmark of cancer. Preliminary data also suggest that the function of this and other chaperones is altered in cancer cells, thereby perturbing histone dynamics and causing genetic and epigenetic instability. Together these data lead us to hypothesise that improper histone chaperone function promotes cancer formation and may be an important prognostic or diagnostic patient tumour marker.

The aim of this project is to evaluate the histone chaperone expression in human cancer samples to determine their value as prognostic or diagnostic markers. The project will involve the validation and use of immunohistochemical, protein gel electrophoresis and quantitative RT-PCR assays for measuring histone chaperone expression in patient tumour samples and statistical analysis to correlate expression with patient clinical data.

2) How are histone proteins regulated in vivo during development and cellular differentiation?

The genome in all nucleated eukaryotic cells is packaged with histone proteins into chromatin. Since all transactions with DNA occur in the context of chromatin, histones play an intimate role in regulating genome function and integrity. Histones occur in a variety of ‘flavours’ (variants) and can be post-translationally modified, encoding a layer of chromatin-based ‘epigenetic’ information that regulates gene expression, superimposed on that encoded by the DNA. Differences in chromatin organisation allow the same genetic code to be ‘read’ (expressed) in different ways to produce the multitude of different cell types throughout one’s body. Indeed during development and cellular differentiation, chromatin is dynamic reorganised and histones have been described to be in a ‘hyperdynamic’ state. A key question is how the dynamics and metabolism of histones are carefully regulated to maintain chromatin plasticity in stem cells and ensure chromatin is properly reorganised during differentiation.

At all points in the cellular life of histones when they are not a part of chromatin, they are escorted by a network of proteins known as histone chaperones. Dr Cook and colleagues recently revealed a novel role for one histone chaperone in regulating the supply of histones (http://pubmed.org/22195965). Our findings raise the intriguing possibility that NASP and its partners play a critical role in stem and differentiating cells, providing an explanation for why NASP is required in the developing embryo.

The aim of this project is to determine the role of NASP and other factors involved in histone metabolism during development using haematopoiesis as a model system. Specifically, you will use retrovirus-mediated RNA interference and mouse bone marrow transplantation to manipulate the histone regulatory network in haematopoietic cells in vivo. Techniques include the production of retroviruses, isolation and transduction of mouse bone marrow cells, transplanation of cells into recipient mice, live animal imaging, flow cytometry and cell culture assays.

3) Mapping the histone interactome in mammalian cells

The eukaryotic genome is packaged with histone proteins into chromatin. Since all transactions with DNA occur in the context of chromatin, proper handling and metabolism of histones throughout their cellular life is critical for genome function and stability.

The majority of cellular histones are part of chromatin, yet a small fraction are soluble and their supply must dynamically respond to changing cellular demands. The principle means by which supply is adjusted is by the modulation of histone synthesis, yet factors which act directly on soluble histones are more suited to dynamic regulation of histone supply. All histones in transit are escorted by a suite of histone chaperone proteins, implicating them in the control of histone supply. Dr Cook and colleagues recently revealed a novel role for one histone chaperone in regulating the supply of histones and obtained the first clue that a lysosomal degradation pathway is involved in histone metabolism (http://pubmed.org/22195965). However, how this degradation pathway and the entire chaperone network operate in a coordinated fashion according to changing cellular demands remains a mystery.

The aim of this project is to develop a high-throughput genome-wide screen to identify novel factors involved in regulating histones and obtain a comprehensive map of the histone interactome. This project will involve a variety of molecular biology techniques (eg. producing DNA constructs for the expression of histones), cell culture, fluorescence microscopy, flow cytometry, immunoprecipitation, Western blotting and the use of automated laboratory robotic equipment.

1) Evaluating histone regulatory proteins as novel prognostic and diagnostic cancer markers

The eukaryotic genome is packaged with histone proteins into chromatin. Since all transactions with DNA occur in the context of chromatin, histones play an intimate role in regulating genome function and integrity. Failure to properly handle histones at any point throughout their cellular ‘life’ can therefore perturb DNA replication, cause genome instability and potentially lead to cancer.

At all points in their cellular life during which they are not a part of chromatin, histones are escorted by a network of proteins known as histone chaperones (http://pubmed.org/23288364;http://pubmed.org/20444609). Dr Cook and colleagues recently revealed a novel role for one histone chaperone in regulating the supply of histones (http://pubmed.org/22195965), in particular during DNA replication stress, a hallmark of cancer. Preliminary data also suggest that the function of this and other chaperones is altered in cancer cells, thereby perturbing histone dynamics and causing genetic and epigenetic instability. Together these data lead us to hypothesise that improper histone chaperone function promotes cancer formation and may be an important prognostic or diagnostic patient tumour marker.

The aim of this project is to evaluate the histone chaperone expression in human cancer samples to determine their value as prognostic or diagnostic markers. The project will involve the validation and use of immunohistochemical, protein gel electrophoresis and quantitative RT-PCR assays for measuring histone chaperone expression in patient tumour samples and statistical analysis to correlate expression with patient clinical data.

2) How are histone proteins regulatedin vivoduring development and cellular differentiation?

The genome in all nucleated eukaryotic cells is packaged with histone proteins into chromatin. Since all transactions with DNA occur in the context of chromatin, histones play an intimate role in regulating genome function and integrity. Histones occur in a variety of ‘flavours’ (variants) and can be post-translationally modified, encoding a layer of chromatin-based ‘epigenetic’ information that regulates gene expression, superimposed on that encoded by the DNA. Differences in chromatin organisation allow the same genetic code to be ‘read’ (expressed) in different ways to produce the multitude of different cell types throughout one’s body. Indeed during development and cellular differentiation, chromatin is dynamic reorganised and histones have been described to be in a ‘hyperdynamic’ state. A key question is how the dynamics and metabolism of histones are carefully regulated to maintain chromatin plasticity in stem cells and ensure chromatin is properly reorganised during differentiation.

At all points in the cellular life of histones when they are not a part of chromatin, they are escorted by a network of proteins known as histone chaperones. Dr Cook and colleagues recently revealed a novel role for one histone chaperone in regulating the supply of histones (http://pubmed.org/22195965). Our findings raise the intriguing possibility that NASP and its partners play a critical role in stem and differentiating cells, providing an explanation for why NASP is required in the developing embryo.

The aim of this project is to determine the role of NASP and other factors involved in histone metabolism during development using haematopoiesis as a model system. Specifically, you will use retrovirus-mediated RNA interference and mouse bone marrow transplantation to manipulate the histone regulatory network in haematopoietic cellsin vivo. Techniques include the production of retroviruses, isolation and transduction of mouse bone marrow cells, transplanation of cells into recipient mice, live animal imaging, flow cytometry and cell culture assays.

3) Mapping the histone interactome in mammalian cells

The eukaryotic genome is packaged with histone proteins into chromatin. Since all transactions with DNA occur in the context of chromatin, proper handling and metabolism of histones throughout their cellular life is critical for genome function and stability.

The majority of cellular histones are part of chromatin, yet a small fraction are soluble and their supply must dynamically respond to changing cellular demands. The principle means by which supply is adjusted is by the modulation of histone synthesis, yet factors which act directly on soluble histones are more suited to dynamic regulation of histone supply. All histones in transit are escorted by a suite of histone chaperone proteins, implicating them in the control of histone supply. Dr Cook and colleagues recently revealed a novel role for one histone chaperone in regulating the supply of histones and obtained the first clue that a lysosomal degradation pathway is involved in histone metabolism (http://pubmed.org/22195965). However, how this degradation pathway and the entire chaperone network operate in a coordinated fashion according to changing cellular demands remains a mystery.

The aim of this project is to develop a high-throughput genome-wide screen to identify novel factors involved in regulating histones and obtain a comprehensive map of the histone interactome. This project will involve a variety of molecular biology techniques (eg. producing DNA constructs for the expression of histones), cell culture, fluorescence microscopy, flow cytometry, immunoprecipitation, Western blotting and the use of automated laboratory robotic equipment.

1) Evaluating histone regulatory proteins as novel prognostic and diagnostic cancer markers

The eukaryotic genome is packaged with histone proteins into chromatin. Since all transactions with DNA occur in the context of chromatin, histones play an intimate role in regulating genome function and integrity. Failure to properly handle histones at any point throughout their cellular ‘life’ can therefore perturb DNA replication, cause genome instability and potentially lead to cancer.

At all points in their cellular life during which they are not a part of chromatin, histones are escorted by a network of proteins known as histone chaperones (http://pubmed.org/23288364;http://pubmed.org/20444609). Dr Cook and colleagues recently revealed a novel role for one histone chaperone in regulating the supply of histones (http://pubmed.org/22195965), in particular during DNA replication stress, a hallmark of cancer. Preliminary data also suggest that the function of this and other chaperones is altered in cancer cells, thereby perturbing histone dynamics and causing genetic and epigenetic instability. Together these data lead us to hypothesise that improper histone chaperone function promotes cancer formation and may be an important prognostic or diagnostic patient tumour marker.

The aim of this project is to evaluate the histone chaperone expression in human cancer samples to determine their value as prognostic or diagnostic markers. The project will involve the validation and use of immunohistochemical, protein gel electrophoresis and quantitative RT-PCR assays for measuring histone chaperone expression in patient tumour samples and statistical analysis to correlate expression with patient clinical data.

2) How are histone proteins regulatedin vivoduring development and cellular differentiation?

The genome in all nucleated eukaryotic cells is packaged with histone proteins into chromatin. Since all transactions with DNA occur in the context of chromatin, histones play an intimate role in regulating genome function and integrity. Histones occur in a variety of ‘flavours’ (variants) and can be post-translationally modified, encoding a layer of chromatin-based ‘epigenetic’ information that regulates gene expression, superimposed on that encoded by the DNA. Differences in chromatin organisation allow the same genetic code to be ‘read’ (expressed) in different ways to produce the multitude of different cell types throughout one’s body. Indeed during development and cellular differentiation, chromatin is dynamic reorganised and histones have been described to be in a ‘hyperdynamic’ state. A key question is how the dynamics and metabolism of histones are carefully regulated to maintain chromatin plasticity in stem cells and ensure chromatin is properly reorganised during differentiation.

At all points in the cellular life of histones when they are not a part of chromatin, they are escorted by a network of proteins known as histone chaperones. Dr Cook and colleagues recently revealed a novel role for one histone chaperone in regulating the supply of histones (http://pubmed.org/22195965). Our findings raise the intriguing possibility that NASP and its partners play a critical role in stem and differentiating cells, providing an explanation for why NASP is required in the developing embryo.

The aim of this project is to determine the role of NASP and other factors involved in histone metabolism during development using haematopoiesis as a model system. Specifically, you will use retrovirus-mediated RNA interference and mouse bone marrow transplantation to manipulate the histone regulatory network in haematopoietic cellsin vivo. Techniques include the production of retroviruses, isolation and transduction of mouse bone marrow cells, transplanation of cells into recipient mice, live animal imaging, flow cytometry and cell culture assays.

3) Mapping the histone interactome in mammalian cells

The eukaryotic genome is packaged with histone proteins into chromatin. Since all transactions with DNA occur in the context of chromatin, proper handling and metabolism of histones throughout their cellular life is critical for genome function and stability.

The majority of cellular histones are part of chromatin, yet a small fraction are soluble and their supply must dynamically respond to changing cellular demands. The principle means by which supply is adjusted is by the modulation of histone synthesis, yet factors which act directly on soluble histones are more suited to dynamic regulation of histone supply. All histones in transit are escorted by a suite of histone chaperone proteins, implicating them in the control of histone supply. Dr Cook and colleagues recently revealed a novel role for one histone chaperone in regulating the supply of histones and obtained the first clue that a lysosomal degradation pathway is involved in histone metabolism (http://pubmed.org/22195965). However, how this degradation pathway and the entire chaperone network operate in a coordinated fashion according to changing cellular demands remains a mystery.

The aim of this project is to develop a high-throughput genome-wide screen to identify novel factors involved in regulating histones and obtain a comprehensive map of the histone interactome. This project will involve a variety of molecular biology techniques (eg. producing DNA constructs for the expression of histones), cell culture, fluorescence microscopy, flow cytometry, immunoprecipitation, Western blotting and the use of automated laboratory robotic equipment.

International links

France

(Institut Curie / CNRS UMR218) G. Almouzni (Chromatin Dynamics Group)

Selected grants

2014

  • Cell division's influence on antibody-mediated immunity; Jolly C, Cook A; National Health and Medical Research Council (NHMRC)/Project Grants.
  • Protease therapies for diabetes-associated liver disease; Gorrell M, Keane F, Cook A, Shackel N, Seth D, Chen J, Jolly C, Hare N, McCaughan G; Rebecca L Cooper Medical Research Foundation/Equipment Grant.

2008

  • Investigating the function of the histone chaperone NASP; Cook A; National Health and Medical Research Council (NHMRC)/Early Career Fellowships (ECF).

Selected publications

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Journals

  • Cook, A., Gurard-Levin, Z., Vassias, I., Almouzni, G. (2011). A Specific Function for the Histone Chaperone NASP to Fine-Tune a Reservoir of Soluble H3-H4 in the Histone Supply Chain. Molecular Cell, 44(6), 918-927. [More Information]
  • Baldeyron, C., Soria, G., Roche, D., Cook, A., Almouzni, G. (2011). HP1alpha recruitment to DNA damage by p150CAF-1 promotes homologous recombination repair. The Journal of Cell Biology, 193(1), 81-95. [More Information]
  • Sharbeen, G., Cook, A., Lau, K., Raftery, J., Yee, C., Jolly, C. (2010). Incorporation of dUTP does not mediate mutation of A:T base pairs in Ig genes in vivo. Nucleic Acids Research, 38(22), 8120-8130. [More Information]
  • Jolly, C., Cook, A., Manis, J. (2008). Fixing DNA breaks during class switch recombination. The Journal of Experimental Medicine, 205(3), 509-513. [More Information]
  • Quivy, J., Gerard, A., Cook, A., Roche, D., Almouzni, G. (2008). The HP1-p150/CAF-1 interaction is required for pericentric heterochromatin replication and S-phase progression in mouse cells. Nature Structural and Molecular Biology, 15(9), 972-979. [More Information]
  • Cook, A., Raftery, J., Lau, K., Jessup, A., Harris, R., Takeda, S., Jolly, C. (2007). DNA-Dependent Protein Kinase Inhibits AID-Induced Antibody Gene Conversion. PLoS Biology, 5(4), 1-8. [More Information]
  • Jolly, C., Cook, A., Raftery, J., Jones, M. (2007). Measuring bidirectional mutation. Journal of Theoretical Biology, 246, 267-277. [More Information]
  • Groth, A., Corpet, A., Cook, A., Roche, D., Bartek, J., Lukas, J., Almouzni, G. (2007). Regulation of replication fork progression through histone supply and demand. Science, 318(1), 1928-1931. [More Information]
  • Cook, A., Oganesian, L., Harumal, P., Basten, A., Brink, R., Jolly, C. (2003). Reduced switching in SCID B cells is associated with altered somatic mutation of recombined S regions. Journal of Immunology, 171(2003), 6456-6464.

Conferences

  • Cook, A., Gurard-Levin, Z., Vassias, I., Almouzni, G. (2012). A specific function for the histone chaperone NASP to fine-tune a reservoir of soluble H3-H4 in the histone supply chain. Lorne Genome Conference 2012, Lorne, VIC, Australia.
  • Cook, A., Gurard-Levin, Z., Vassias, I., Almouzni, G. (2010). Modulation of the soluble pool of histone H3-H4 by the histone chaperone NASP. 75th Symposium - Nuclear Organization and Function, 75th Symposium - Nuclear Organization and Function: Cold Spring Harbor Laboratory Press.

2012

  • Cook, A., Gurard-Levin, Z., Vassias, I., Almouzni, G. (2012). A specific function for the histone chaperone NASP to fine-tune a reservoir of soluble H3-H4 in the histone supply chain. Lorne Genome Conference 2012, Lorne, VIC, Australia.

2011

  • Cook, A., Gurard-Levin, Z., Vassias, I., Almouzni, G. (2011). A Specific Function for the Histone Chaperone NASP to Fine-Tune a Reservoir of Soluble H3-H4 in the Histone Supply Chain. Molecular Cell, 44(6), 918-927. [More Information]
  • Baldeyron, C., Soria, G., Roche, D., Cook, A., Almouzni, G. (2011). HP1alpha recruitment to DNA damage by p150CAF-1 promotes homologous recombination repair. The Journal of Cell Biology, 193(1), 81-95. [More Information]

2010

  • Sharbeen, G., Cook, A., Lau, K., Raftery, J., Yee, C., Jolly, C. (2010). Incorporation of dUTP does not mediate mutation of A:T base pairs in Ig genes in vivo. Nucleic Acids Research, 38(22), 8120-8130. [More Information]
  • Cook, A., Gurard-Levin, Z., Vassias, I., Almouzni, G. (2010). Modulation of the soluble pool of histone H3-H4 by the histone chaperone NASP. 75th Symposium - Nuclear Organization and Function, 75th Symposium - Nuclear Organization and Function: Cold Spring Harbor Laboratory Press.

2008

  • Jolly, C., Cook, A., Manis, J. (2008). Fixing DNA breaks during class switch recombination. The Journal of Experimental Medicine, 205(3), 509-513. [More Information]
  • Quivy, J., Gerard, A., Cook, A., Roche, D., Almouzni, G. (2008). The HP1-p150/CAF-1 interaction is required for pericentric heterochromatin replication and S-phase progression in mouse cells. Nature Structural and Molecular Biology, 15(9), 972-979. [More Information]

2007

  • Cook, A., Raftery, J., Lau, K., Jessup, A., Harris, R., Takeda, S., Jolly, C. (2007). DNA-Dependent Protein Kinase Inhibits AID-Induced Antibody Gene Conversion. PLoS Biology, 5(4), 1-8. [More Information]
  • Jolly, C., Cook, A., Raftery, J., Jones, M. (2007). Measuring bidirectional mutation. Journal of Theoretical Biology, 246, 267-277. [More Information]
  • Groth, A., Corpet, A., Cook, A., Roche, D., Bartek, J., Lukas, J., Almouzni, G. (2007). Regulation of replication fork progression through histone supply and demand. Science, 318(1), 1928-1931. [More Information]

2003

  • Cook, A., Oganesian, L., Harumal, P., Basten, A., Brink, R., Jolly, C. (2003). Reduced switching in SCID B cells is associated with altered somatic mutation of recombined S regions. Journal of Immunology, 171(2003), 6456-6464.

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