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Manchester Centre for Integrative Systems Biology

Dr. Chris Knight


 

Address

 

(Room B.2012)

Faculty of Life Sciences

Michael Smith Building

University of Manchester

Oxford Road

Manchester M13 9PT

UK

 

Telephone

 

+44 (0) 161 275 5378

 

email

 

chris.knight@manchester.ac.uk

 

Alternative website Including PhD projects

chris

 

 

 

 

 

 

 

Research Interests

 

The genotype-phenotype map in evolution

How do the individual DNA changes used by evolution (genotype) affect the behaviour of the complex system that is the living cell (phenotype)? How do organisms manage to evolve at all when even a small genetic change may affect many different aspects of the cellular system? How do the DNA changes used by short-term evolution relate to the DNA changes seen across longer-term evolution across strains or species?

To explore the answers to such questions I use a variety of approaches including:

  • microbial experimental evolution, combining the power of 'model' genetic systems and with “'omic” technologies for measuring many aspects of phenotype at the same time.
  • Bioinformatic analysis of fully sequenced genomes to look at sequence evolution across longer time-scales.
  • in silico evolution where DNA sequences evolved in a computer are tested experimentally. Looking at the genotype-phenotype map in such an abstracted system makes it possible to control all aspects of the evolution and look at many thousands of DNA sequences.


yeast systems biology

'Systems Biology' is a buzz word, often referring to the large communal efforts being put into building complex mathematical models of cellular processes. I have links with one such effort by the Manchester Centre for Integrative Systems Biology, creating an experimentally parameterized model of yeast metabolism. I have a particular interest in understanding how 'the system' can be defined in a biologically meaningful way.


modelling

All of the above requires appropriate ways to abstract meaningful insights from complex biological systems. This requires mathematical or statistical models. What is the appropriate level of complexity for such models? How can the results of very complex models be analysed, visualised and interpreted meaningfully? These questions cut across all my work, but particularly concern:


  • network models of “'omic” data
  • Models of experimentally evolved genealogies
  • climate models, analysing data from the climateprediction.net project to see how uncertain or variable aspects of the model affect outputs relevant to predicting climate change.

 

Research Funding

 

Research Career Development Fellowship from the Wellcome Trust 2008-2012


Evolution as an Information Dynamic System from the EPSRC 2010-2012


 

Bio

 

2008-present

University of Manchester, Faculty of Life Sciences

Wellcome Trust Research Career Development Fellow


2005-2007

University of Manchester, Manchester Interdisciplinary Biocentre

Post-doc in yeast systems biology: funded by the BBSRC with Douglas Kell.


2002-2005

University of Oxford, department of Plant Sciences

Postdoc on the molecular basis of evolution in the bacterium Pseudomonas fluorescens. Funded by NERC with Paul Rainey also with the proteomics lab in the department of Biochemistry.


1997-2001

Imperial College London at Silwood Park

PhD on ‘The genetics and evolution of body size in the nematode Caenorhabditis elegans’ funded by NERC, supervised by Armand Leroi


1994-1996

Christ's College Cambridge

MA Natural Sciences, finalising in genetics

 

Publications

 

peer reviewed

 

Knight, C. G. , X. X. Zhang, A. Gunn, T. Brenner, R. W. Jackson, S. R. Giddens, S. Prabhakar, N. Zitzmann, P. B. Rainey (2010). Testing temperature-induced proteomic changes in the plant-associated bacterium Pseudomonas fluorescens SBW25. Environmental Microbiology Reports 31, 1080-1090. (link, pdf)

 

Knight, C. G. and J.W. Pinney (2009). Making the right connections: biological networks in the light of evolution. Bioessays 31, 1080-1090. (link, pdf)

 

Silby, M. W.; Cerdeno-Tarraga, A. M.; Vernikos, G. S.; Giddens, S. R.; Jackson, R. W.; Preston, G. M.; Zhang, X.; Moon, C. D.; Gehrig, S.; Godfray, H. C.; Knight, C. G.; Malone, J.; Robinson, Z.; Spiers, A.; Harris, S.; Challis, G. L.; Yaxley, A. M.; Harris, D.; Seeger, K.; Murphy, L.; Rutter, S.; Squares, R.; Quail, M.; Saunders, E.; Mavromatis, K.; Brettin, T. S.; Bentley, S. D.; Hothersall, J.; Stephens, E.; Thomas, C. M.; Parkhill, J.; Levy, S. B.; Rainey, P. B.; Thomson, N. R. (2009) Genomic and functional analyses of diversity and plant interactions of Pseudomonas fluorescens . Genome Biology 10, R51. (link, pdf)

 

Knight, C. G. , Platt M, Rowe W, Wedge DC, Khan F, Day P, McShea A, Knowles J, Kell DB (2009). Array-based evolution of DNA aptamers allows modeling of an explicit sequence-fitness landscape . Nucleic Acids Research 37, e6. (link, pdf)

 

Jones, J., Studholme, D. J., Knight, C. G. & Preston, G. M. (2007) Integrated bioinformatic and phenotypic analysis of RpoN-dependent traits in the plant growth-promoting bacterium Pseudomonas fluorescens SBW25 Environmental Microbiology 9, 3046-3064. (link, pdf)

 

Knight, C. G. , Knight, S. H. E., Massey, N., Aina, T., Christensen, C., Frame, D. J., Kettleborough, J. A., Martin, A., Peascoe, S., Sanderson, B., Stainforth, D., Allen, M. (2007). Association of parameter, software and hardware variation with large scale behaviour across 57,000 climate models . Proceedings of the National Academy of Sciences of the United States of America 104, 12259-12264. (link, pdf)

 

Bantanaki, E., Kassen, R., Knight, C.G ., Robinson, Z., Spiers, A. & Rainey, P. (2007) Adaptive divergence in experimental populations of Pseudomonas fluorescens III. Mutational origins of wrinkly spreader diversity . Genetics 176, 441-453 (link, pdf)

 

Knight, C. G. , Zitzmann, N., Prabhakar, S., Hebestreit, H. F., and Rainey, P. B. (2006). Unraveling adaptive evolution: how a single point mutation affects the protein co-regulation network. Nature Genetics 38, 1015-1022. (link, pdf,raw data) [News and Views: Remold, S. K. (2006). Protein expression tells only half the story. Nature Genetics 38 , 979-980 (link, pdf)]

 

Beaumont, H. J. E., Gehrig, S. M., Kassen, R., Knight, C. G. , Malone, J., Spiers, A. J., and Rainey, P. B. (2006). The genetics of phenotypic innovation. In Prokaryotic Diversity: Mechanisms and Significance (Society for General Microbiology Symposium 66), N. A. Logan, H. M. Lappin-Scott, and P. C. F. Oyston, eds. ( Cambridge , Cambridge University Press), 91-104. (link,)

 

Knight, C. G. , and Beale, C. M. (2005). Pale Rock Sparrow Carpospiza brachydactyla in the Mount Lebanon range: modelling breeding habitat. Ibis 147 , 324-333. (link, pdf)

 

Knight, C. G. , Kassen, R., Hebestreit, H. F., and Rainey, P. B. (2004). Global analysis of predicted proteomes: Functional adaptation of physical properties . Proceedings of the National Academy of Sciences of the United States of America 101 , 8390-8395. (link, pdf) [Commentary: Broccieri, L. (2004). Environmental signatures in proteome properties. PNAS 101 , 8257-8258. (link, pdf)]

 

Knight, C. G. , and Beale, C. M. (2004). Breeding habitat of the Pale Rock Sparrow Carpospiza brachydactyla in the Mount Lebanon range. Sandgrouse 26 , 127-131. (pdf)

 

Patel, M. N., Knight, C. G. , Karageorgi, C., and Leroi, A. M. (2002). Evolution of germ-line signals that regulate growth and aging in nematodes . Proceedings of the National Academy of Sciences of the United States of America 99 , 769-774. (link, pdf)

 

Knight, C. G. , Patel, M. N., Azevedo, R. B. R., and Leroi, A. M. (2002). A novel mode of ecdysozoan growth in Caenorhabditis elegans . Evolution & Development 4 , 16-27. (link, pdf)

 

Knight, C. G. (2001) The genetics and evolution of body size in the nematode Caenorhabditis elegans, Imperial College , London .

 

Knight, C. G. , Azevedo, R. B. R., and Leroi, A. M. (2001). Testing life-history pleiotropy in Caenorhabditis elegans . Evolution 55 , 1795-1804. (pdf)


book review

Knight, C. G. (2010). Book Review: Elements of Computational Systems Biology. Eds. H.M. Lodhi & S. Muggleton. Wiley-Blackwell . Genome Research 92, 324-325. (link, pdf)


'popular'

Knight, C. G. (2010). Darwin:Bane or blessing? Faith and Thought 49, 12-21. (Journal Site, pdf)

 

Knight, C. G. (2010). Curing the climate? Physics Education 45, 13-17. (link, pdf)

 

Knight, C. G. (2004). Storia di un verme. Kos: Rivista di medicina, cultura e scienze umane 231, 60-63. [Italian translation of this]