9 / 26
Page 27
Notes:
allied
academies
J Pharmacol Ther Res 2017 Volume 1 Issue 2
November 02-03, 2017 Chicago, USA
4
th
International Congress on
International Conference and Exhibition on
Drug Discovery, Designing and Development
Biochemistry, Molecular Biology: R&D
&
Physical forces cause
HoxD
gene cluster elongation
Spyros Papageorgiou
National Center for Scientific Research-Demokritos, Greece
H
ox
gene collinearity is a fundamental property in theprocess
of
Hox
gene expression. It correlates the 3’ to 5’ sequential
gene alignment in the
Hox
gene cluster with the ontogenetic
units along the anterior/posterior axis of the embryo. This
property is multiscalar and cannot be treated by biomolecular
mechanisms alone. In multiscale phenomena physical laws
must come into play. The biophysical model (BM) provides the
necessary tools for an integratedmultiscalar explanation of
Hox
collinearity. According to BM, physical forces are created which
pull the
Hox
genes sequentially from the compact inactive
Hox
gene cluster toward the transcription factory domain, where
gene transcription is possible. The BM successfully describes
the genetic engineering experiments where some genes of the
vertebrate
Hox
cluster are deleted (or duplicated). Although the
BM was introduced in 2001, it is only in the last 2 years that
it has been adopted by the scientific community, because the
evidence was missing for the existence of such forces. However,
recent instrumental progress in achieving high imaging
resolution (e.g. 3D DNA FISH, STORM etc.) make possible
the confirmation of several BM predictions. For instance, it is
found that the mouse
HoxD
cluster is elongated up to 5-6 times
during
Hox
gene transcription. These unexpected physical
deformations agree with the BMpredictions. New experiments
are proposed to test further the biophysical model. A synthesis
of Biophysics and Biochemistry is proposed to explain
Hox
gene
collinearity in two steps: in a first step, the BMforces translocate
the
Hox
genes in the right location for transcription. In a second
step, biomolecular mechanisms transcribe the translocated
genes.
Speaker Biography
Spyros Papageorgiou has graduated in Physics from the Athens University, Greece.
He has received his DPhil in Theoretical Physics from Oxford and Sussex Universities
in 1965. He was a Research Fellow at Theory Division of CERN 1968-1970 and a
Corresponding Fellow between CERN and Demokritos, Greece 1970-1973. In 1976,
he started working on models in Developmental Biology. He formulated models in
reaction-diffusion, pattern regulation, regeneration, gene expression etc. In 2000, he
became Emeritus Research Director at ‘Demokritos’ and he currently study the
Hox
gene collinearity problem. He formulated the biophysical model (BM) (S Papageorgiou,
BIOLOGY 2017,6, 32) based on the hypothesis of physical forces translocating the
Hox
genes toward the transcription factory domain where transcription is possible.
e:
spapage@bio.demokritos.gr