Forsdyke Laboratory of Bioinformatics
and Theoretical Biology
Recent
Collaborators
Research
Projects
(Bioinformatics-Genomics/Theoretical Biology)
Recent
Publications (Bioinformatics-Genomics/Theoretical Biology)
Past Projects (Molecular Biology)
Publications
(Molecular Biology)
Forsdyke HomePage (AIDS,
Bioinformatics, Evolution,
Theoretical Immunology, X Chromosomes)
| Keywords: Bioinformatics,
Genomics, Theoretical Biology,
Speciation, AIDS, Isochores, Evolution, Biohistory, Darwin, Romanes, Bateson,
Goldschmidt, Chargaff, Wada, G0/G1 switch genes (G0S genes), Immunology,
Malaria |
Department of Biochemistry, Botterell
Hall, Queen's University, Kingston, Ontario, Canada, K7L3N6.
- Donald Forsdyke is at 613-533-2980
-
forsdyke@post.queensu.ca
|
-
-
- Recent Collaborators:
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- Dr. Anthony D. Cristillo
NIH (1998-2002). Advanced BioScience Laboratories, Maryland, USA (2002- )
- Dr. Scott P. Heximer (St. Louis, Mo,
1997-2002). Assist. Prof. at Department of Physiology, Univ. Toronto
(2003- )
- LaVerne Russell (Technical assistant, 1979-1997)
- Sheldon Bell 1996. (Undergraduate student. To software design for banking
systems)
- Labonnie Biswas 1995. (Undergraduate student. For Graduate Studies, U. of
Toronto)
- Kha Dang 1997.(Undergraduate student. To further education)
- Previn Dutt 1997. (Undergraduate student. To Graduate Studies in Biochemistry,
Queen's)
- Tim Lillicrap 1997 (High School student)
- Janet Ho 1997. (Undergraduate student. Graduate Studies in Biochemistry,
Queen's)
- Y.C.(Derek) Chow 1997. (Undergraduate student. To Dental
School)
- Isabelle Barrette 1998. (Undergraduate student. M.Sc. in Bioinformatics, U. of Montreal,
and on to graduate studies at U. of Alberta)
Sean McKenna 1998 (Undergraduate student. Graduate studies at U. of
Alberta)
David. R. Taylor 1998 (Undergraduate student. To Medical
School)
- Perry J. Lao 1999. (Undergraduate student. To Law School)
Gregory Hill 1999. (Undergraduate student. To start own software
company.)
Robert Rasile 1999. (Undergraduate student. To further
education.)
James R. Mortimer 2000. (Undergraduate student. To bioinformatics with
Merck-Frosst.)
- Theresa M. St. Denis 2000. (Undergraduate student. To
MJS
BioLynx Inc.)
- Alexander K. Schramm 2000. (Undergraduate student. To
medical school)
- Robin Lambros 2000. (Undergraduate
student. To biotech. industry)
- Chris Madill 2000-1 (Undergraduate
student) To Molecular Mining Inc., Kingston and then to Grad. studies at
Hosp. for Sick Children, Toronto
- Scott. D. Smith 2001. (Undergraduate student)
To Grad. studies as Hosp. for Sick Children, Toronto
H. Y. (Joanne) Xue 2002. (Undergraduate student). To
Grad studies at University of Toronto.
S-J. (Jessica) Lee 2002. (Undergraduate student).
To Grad studies at University of BC.
- Justin LeBlanc 2003. (Undergraduate student).
To Grad studies at University of BC.
-
-
Projects
(Bioinformatics/Genomics/Theoretical Biology)
- Self/Not-self discrimination (extracellular and intracellular)
- Speciation, Haldane's Rule
- X-chromosome dosage compensation
- Evolution of genetic dominance
- Locating genes in uncharted sequences (a "Rosetta Stone"
for DNA?)
- Folding of randomized-sequence difference analysis
- Chargaff difference analysis: purine-loading of RNAs
- Role of CHI sequences in recombination
- Origin of Introns, "Junk" DNA and low
complexity elements
- Isochores (micro and macro)
- Conflict between different forms of information in
selected genes/genomes:
- G0S genes
- MHC genes
- Retroviruses (HIV, HTLV)
- Herpes simplex virus
- Epstein-Barr virus
- Kaposi's Sarcoma-associated virus (HHV8)
- Plasmodium falciparum
- Vaccinia virus
- Saccharomyces cerevisiae (chromosome III)
- Bithorax complex (Drosophila melanogaster)
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- Recent Publications
(Bioinformatics/Genomics/Theoretical
Biology)
Lee, S.-J., Mortimer, J. R. & Forsdyke, D. R. (2004) Applied
Bioinformatics.3, 219-228. Genomic Conflict Settled in Favour of
the Species Rather than of the Gene at Extreme GC% Values.(Click here for full text)
Forsdyke, D. R. (2004) J. Biological
Systems 12, 261-271. Regions of Relative GC% Uniformity are
Recombinational Isolators. (Click here for full text)
Forsdyke, D. R. (2004) J. Theor.
Biol. 230, 189-196. Chromosomal Speciation: A Reply. (Click here for full text)
Forsdyke, D. R.(2004) Historic
Kingston 52, 95-103. Grant Allen, George Romanes,
Stephen Jay Gould and the evolution establishments of their times. (Click here for full text)
Forsdyke, D. R. & Bell, S. J. (2004) Applied
Bioinformatics 3, 3-8. Purine-loading, stem-loops, and Chargaff's second parity
rule: a discussion of the application of elementary principles to early chemical observations. (Click here for full text)
Forsdyke, D. R. (2003) J.
Biological Systems 11, 341-350. William Bateson,
Richard Goldschmidt, and non-genic modes of speciation.(Click here for full text)
Lambros, R. J., Mortimer, J. R. & Forsdyke, D. R.(2003)
Extremophiles 7, 443-450. Optimum growth
temperature and the base composition of open reading frames in prokaryotes.(Click here for full text)
Mortimer, J. R. & Forsdyke, D. R.(2003)
Applied
Bioinformatics 2, 47-62. Comparison of responses by
bacteriophage and bacteria to pressures on the base composition of open
reading frames. (Click here for full text)
Xue, H. Y. & Forsdyke, D. R. (2003) Mol. Biochem.
Parasitol. 128, 21-32. Low complexity segments in Plasmodium
falciparum proteins are primarily nucleic acid level adaptations. (Click here for full text)
Forsdyke, D. R., Madill, C. A., & Smith, S. D. (2002) Trends
Immunol. 23, 575-579. Immunity as a function of the unicellular
state: implications of emerging genomic data.(Click here for full text)
Forsdyke, D. R. (2002) Trends
Parasitol. 18, 411-418. Selective pressures that decrease
synonymous mutations in Plasmodium falciparum.(Click here for full text)
Forsdyke, D. R. (2002) Bioinformatics
18, 215-217. Symmetry observations in long nucleotide sequences. (Click
here for full text)
Forsdyke, D. R. (2001) J. Theor. Biol.
21, 425-434. Adaptive value of polymorphism in intracellular self/not-self
discrimination. (Click here for
full text)
Barrette, I. H., McKenna, S., Taylor, D. R. & Forsdyke, D. R. (2001) Gene
270, 181-189. Introns resolve the conflict between base order-dependent
stem-loop potential and the encoding of RNA or Protein: Further evidence from
overlapping genes. (Click here for
full text)
Cristillo, A.D., Mortimer, J. R., Barrette, I. H.,
Lillicrap, T. P. & Forsdyke, D. R. (2001) J.
Theor. Biol. 208, 475-491. Double-stranded RNA as a
not-self alarm signal: to evade, most viruses purine-load their RNAs, but some (HTLV-1,
Epstein-Barr) pyrimidine-load. (Click here for
full text)
Forsdyke, D. R. & Mortimer, J. R. (2000) Gene
261, 127-137. Chargaff's legacy. (Click here for full text)
Forsdyke, D. R. (2000) J.
Theor. Biol. 204, 443-452.
Haldane's rule: hybrid sterility affects the heterogametic sex first because sexual
differentiation is on the path to species differentiation. (Click
here for full text)
Lao, P. J. & Forsdyke, D. R. (2000a) Genome
Res. 10, 228-236.Thermophilic
bacteria strictly obey Szybalski's transcription direction rule and politely purine-load
RNAs with both adenine and guanine. (Click
here for full text)
Lao, P. J. & Forsdyke, D. R. (2000b) Gene 243, 47-57. Crossover hotspot instigator (Chi) sequences in E.
coli occupy distinct recombination/transcription islands.(Click here for full text)
- Bell, S. J. & Forsdyke, D. R. (1999a) J. Theor. Biol. 197, 51-61. Accounting Units in DNA. (Click here
for full text)
- Bell, S. J. & Forsdyke, D. R. (1999b) J.
Theor. Biol. 197,
63-76. Deviations from Chargaff's second parity rule correlate with direction of
transcription. (Click
here for full text)
Forsdyke, D. R. (1999a) Cell Stress
& Chaperones 4,
205-210. Heat shock proteins as mediators of aggregation-induced "danger"
signals: implications of the slow evolutionary fine-tuning of sequences for the
antigenicity of cancer cel1. (Click
Here for full text)
Forsdyke, D. R. (1999b) J. Theor.
Biol. 201, 47-61. Relationship
of Romanes' "intrinsic" variability of the reproductive system, and Bateson's
"residue", to the species-dependent component of the base composition, (C+G)%. (Click Here for full
text)
- Forsdyke, D. R. (1999c) Queen's
Quarterly.106, no. 1. 112-134. The
Origin of Species, Revisited. (Click
here for full text)
- Bell, S. J., Chow, Y. C., Ho, J. Y. K., and Forsdyke, D. R. (1998) Gene 216,
285-292. Correlation of Chi orientation with transcription indicates a fundamental
relationship between recombination and transcription.(Click here for full text)
- Dang, K. D., Dutt, P. B., and Forsdyke, D. R. (1998) Biochem. Cell Biol. 76, 129-137. Chargaff differences correlate with transcription
direction in the bithorax complex of Drosophila. (Click
Here for full text)
- Forsdyke, D.R. (1998). J. Theor. Biol. 192, 489-504. An alternative way of thinking about stem-loops
in DNA. A case study of the G0S2 gene. (Click here for full text)
- Forsdyke, D. R. (1996a) Immunogenetics 43, 182-189. Stem-loop potential in MHC
genes: a new way of evaluating positive Darwinian selection.(Click here for full text)
- Forsdyke, D. R. (1996b) J. Theoret.
Biol. 178, 405-417. Different
biological species "broadcast" their DNAs at different (G+C)%
"wavelengths".(Click
here for full text)
- Forsdyke, D.R. (1995a) J. Biol.
Systems. 3, 273-287. Entropy-driven
protein self-aggregation as the basis for self/not-self discrimination in the crowded
cytosol.(Click
here for full text)
- Forsdyke, D.R. (1995b) J. Theoret.
Biol. 172,
335-345. Fine-tuning of intracellular protein concentrations, a collective protein
function involved in aneuploid lethality, sex determination and speciation?(Click
here for full text)
- Forsdyke, D.R. (1995c) Mol. Biol. Evol. 12, 949-958. A stem-loop "kissing" model for the
initiation of recombination and the origin of introns.(Click here for full text)
- Forsdyke, D. R. (1995d) Mol. Biol. Evol. 12, 1157-1165.Conservation of stem-loop potential in introns
of snake venom phospholipase A2 genes: an application of FORS-D analysis. (Click here for full text)
- Forsdyke, D. R. (1995e) J. Mol. Evol. 41, 573-581. Relative
roles of primary sequence and (G+C)% in determining the hierarchy of frequencies of
complementary trinucleotide pairs in DNAs of different species. (Click here for full text)
- Forsdyke, D. R. (1995f) J. Mol. Evol. 41, 582-586.Sense in antisense? (Click here for full text)
- Forsdyke, D. R. (1995g) J. Mol. Evol. 41, 1022-1037. Reciprocal relationship between stem-loop
potential and substitution density in retroviral quasispecies under positive Darwinian
selection. (Click here for full text)
- Forsdyke, D. R. (1994a) J. Theor. Biol. 167, 1-6. The heat-shock response and
the molecular basis of genetic dominance. (Click
here for full text)
- Forsdyke, D. R. (1994b) J. Theor. Biol. 167, 7-12.Relationship of X chromosome dosage compensation to
intracellular self/not-self discrimination: a resolution of Muller's paradox? (Click
here for full text)
- Past
Projects
(Molecular Biology)
- Peripheral blood mononuclear cells have a high
proportion of T lymphocytes arrested in the
G0 phase of the cell cycle. The cells appear "resting"
or "latent", as are any copies of the HIV genome
they might contain. On activation, the cells "awake"
as does latent HIV. Thus, mechanisms governing lymphocyte "latency"
might also be governing HIV latency.
After activation by the plant lectin, concanavalin A
(Con-A), T lymphocytes enter G1 phase and enlarge, subsequently entering S
phase and dividing. A set of human putative G0/G1 switch regulatory
genes ("G0S" genes)
were identified in our laboratory. The corresponding mRNAs were found to be differentially
expressed in human blood lymphocytes shortly after the addition of Con-A. It was
anticipated that such mRNAs would correspond to proteins involved in orchestrating either
entry into the G1 phase of the cell cycle, or the immediate defence response to
a foreign pathogen. Some of the genes have been found to play a general role in signal
transmisssion, e.g. in the central nervous system.
The 8 genes selected for detailed analysis were G0S2, G0S3,
G0S7, G0S8, G0S9,
G0S19, G0S24
and G0S30. G0S2
is very sensitive to the immunosuppressant,
cyclosporin-A. G0S3 and G0S7 are members of the FOS oncogene
family. G0S8 has been renamed RGS2 (regulator of G-protein signalling
number 2), although it also reacts with adenyl cyclase. G0S19,
which we reported in
1985 as a differentially expressed mRNA, corresponds to the chemokine MIP1alpha
(or CCL3), the receptor for which
(CCR5) turns out to be
a co-receptor for HIV-1. G0S24
regulates the stability of tumor necrosis factor
alpha (TNFalpha), and thus may be
important in AIDS therapy (Click
Here).
G0S30, which we also reported in 1985, corresponds to the
later reported murine EGR1
and rat NGF1A genes. These encode a transcription
factor that regulates TNFalpha and cell senescence,
and is a "gatekeeper" of the
p53 tumor suppressor pathway. Some of the human genes have acquired names
originally applied to the rodent homologs.
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| Human G0 Switch Gene |
Rodent Homolog
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G0S2
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. |
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G0S3/FOSB
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FOSB
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G0S7/FOS
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FOS/TIS28
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G0S8/RGS2
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RGS2
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G0S9/PBEF
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. |
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G0S19/MIP1-alpha/CC3
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MIP1-alpha/LD78-alpha/464.1
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G0S24
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TIS11/NUP475/TTP
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G0S30/EGR1
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EGR1/NGFI-A/TIS8/ZIF-268
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- Recent Publications
(Molecular Biology)
- Heximer, S.P., Cristillo, A.D., Russell, L. and Forsdyke, D.R. (1998) DNA Cell Biol.17,
249-263. Expression and Processing of G0/G1 Switch Gene 24 (G0S24/TIS11/TTP/NUP475) RNA in
Cultured Human Blood Mononuclear Cells.(Click Here)
- Heximer, S.P., Ernst, B.D., Russell, L., and Forsdyke, D.R. (1998) DNA Cell Biol.17,61-68.
The normal copy of the G0S19-associated, CpG island-containing, upstream sequence is
downstream of G0S19-2/MIP1alpha with a TRE17 oncogene.(Click Here)
- Cristillo, A.D., Heximer, S.P., Russell, L., and Forsdyke, D.R. (1997) DNA Cell Biol. 16, 1449-1458. Cyclosporin A Inhibits Early mRNA Expression of
G0/G1 Switch Gene 2 (G0S2) in Cultured Human Blood Mononuclear Cells.(Click Here)
- Heximer, S. P., Cristillo, A. D. & Forsdyke, D. R.(1997) DNA Cell Biol. 16,
589-598. Comparison of mRNA expression of genes regulating G-protein signalling
(RGS1/IR20/BL34 and RGS2/G0S8) in cultured human lymphocytes.(Click Here)
- Heximer, S. P., Cristillo, A. D., Russell, L. & Forsdyke, D. R. (1996)
DNA Cell Biol. 15, 1025-1038. Sequence analysis and expression in cultured
lymphocytes of the human FOSB gene (G0S3).(Click Here)
- Cristillo, A. D., Heximer, S. P. & Forsdyke, D. R. (1996) DNA Cell. Biol. 15,
561-570. A "stealth" approach to inhibition of lymphocyte activation by
oligonucleotides complementary to the putative G0/G1 switch regulatory gene
G0S30/EGR1/ZFP6.(Click Here)
- Wu, H-K., Heng, HHQ., Shi, X-M., Forsdyke, D. R., Tsui, L-C., Mak, T.W., Minden, M. D.
& Siderovski, D. P. (1995) Leukaemia 9, 1291- 1298. Differential expression of a basic
helix-loop-helix phosphoprotein gene, G0S8, in acute leukaemia and localization to human
chromosome 1q31.(Click Here)
- Siderovski, D. P., Heximer, S.P. & Forsdyke, D. R. (1994) DNA Cell Biol. 13,
125-147.A human gene encoding a putative basic helix- loop-helix phosphoprotein whose mRNA
increases rapidly in cycloheximide-treated blood mononuclear cells.(Click Here)
- Heximer, S.P. & Forsdyke, D.R. (1993) DNA Cell Biol. 12,
73-88. A human putative lymphocyte G0/G1 switch gene homologous to a rodent gene encoding
a zinc-binding potential transcription factor.(Click Here)
- Russell, L. & Forsdyke, D.R. (1993) DNA
Cell Biol. 12, 157-175. The third
human homolog of a murine gene encoding an inhibitor of stem cell proliferation is
truncated and linked to a CpG island- containing upstream sequence.(Click Here)
HomePage with Full
Text of Selected Papers,-
- on AIDS, Bioinformatics, Evolution, Theoretical Immunology, X Chromosomes, from
the 19th century onwards, with Commentary. (Click Here)
-
-
- COS Profile of DRF
(Click Here)
This page was initiated in 1998, and last updated 20 Jan 2005, by D. R.
Forsdyke
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Since 30th March 1999