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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]
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