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Joyoti Basu, Indrani
Bose, Manikuntala
Kundu
Stochastic
Gene Expression: Effect
of positive feedback and gene expression noise in mycobacterial
persistence
(see also Phenotypic Heterogeneity):
Indrani
Bose and Rajesh Karmakar
Graded
versus Binary Gene Expression (GE):
Binary
gene expression seen in distribution of protein levels.
- Have
proposed a purely stochastic origin of binary gene expression
consistent with
experimental observations.
- Stochatic
binary GE: no bistability in the deterministic case (See
reviews by Kaern et al., Nature Reviews Genetics 6, 451 (2005); Raj et
al.,
Cell 135, 216 (2008) ).
- Derived
conditions for graded and binary GE in terms of GE parameters
Further
details:
Graded
and
binary
responses
in
stochastic
gene
expression
by
Karmakar
R. and Bose I., Physical
Biology
1,
197 (2004)
Stochastic
Origins of Haploinsufficiency (HI):
- HI:
Genetic disorder brought about by loss
in gene copy number, occurs in diploid organisms. Examples
of HI: certain types of cancer and diabetes
- Reduced
number of genes: larger fluctuations in protein levels
- Finite
probability that level falls
below threshold for onset
of
protein
activity
- Loss
of important protein function: may give rise to diseases
- Have
calculated analytically the probability that a protein level falls
below a
threshold level due to fluctuation
Further
details:
Mathematical
models
of
haploinsufficiency
by
Bose
I.
and
Karmakar
R.
in
Biology
of
Genetic
Dominance
ed.
by
Veitia
R.
(Landes
Bioscience
USA
2006),
page
76
Positive
Feedback,
Stochasticity
and
Genetic
Competence:
Stochastic
simulation of
competence development in a small subpopulation
- Have
developed
a mathematical model to
probe how a fraction of B. subtilis population
develops competence
under stress.
- Have
proposed
three
mechanisms
for
the
development
of
heterogeneity (See review by Veening et al.,
Ann. Rev.
Microbiol. 62, 193 (2008); see also To et al.,
Science 327, 1142 (2010)
for an experimental verification of one of the
mechanisms)
Further
details:
Positive
feedback,
stochasticity
and
genetic
competence
by
Karmakar R. and Bose I., Physical
Biology
4,
29
(2007)
Indrani
Bose and Bhaswar
Ghosh
Noise
Characteristics of Feed Forward Loops:
Four types of coherent feed
forward loops; X, Y, Z denote genes
- Have shown that the
Type-1 coherent feedforward loop (FFL) acts as the best
noise filter amongst the four coherent feed forward loops.
- This particular type
of FFL is the most
abundant FFL in the gene transcription regulatory networks of
E.coli and S.cerevisiae
- Speculation:
noise
is
one
parameter
on
which
natural
evolution
work (See
review
by
Uri
Alon,
Nature
Review Genetics
8, 450 (2007))
Further
details:
Noise
characteristics
of
feed
forward
loops
by
Ghosh
B.,
Karmakar
R.
and
Bose I., Physical Biology 2,
36
(2005)
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