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SUMMARY:Mathematical modelling of potential mechanism for the restoration
of the T-cell homeostasis along with a sustained decay in viral reservoir
upon infusion of CCR5 gene edited T cells in HIV infected subjects
DTSTART;VALUE=DATE-TIME:20180710T010000Z
DTEND;VALUE=DATE-TIME:20180710T013000Z
DTSTAMP;VALUE=DATE-TIME:20240619T111707Z
UID:indico-contribution-50-137@conferences.maths.unsw.edu.au
DESCRIPTION:Speakers: Angie Raad (CDM\, York University \, Toronto\, Cana
da\,)\nAlthough antiretroviral therapy (ART) suppresses viral replication\
, patients still suffer from both low CD4 T-cell counts and HIV persistenc
e\, requiring them to remain on complex ART regimens for life. A naturally
occurring 32-base pair deletion in the CCR5 gene\, the major co-receptor
for HIV entry\, is associated with infection resistance. \n\nIn the study
initiated by Sangamo Therapeutics\, HIV-infected subjects received a singl
e infusion of autologous CCR5-modified CD4 T-cells. Following infusion\, w
e observed a sustained increase in the CD4 T-cells count (mean ~162 cells/
μL) with a significant decrease in the HIV reservoir (median ~1 log 3yrs
post infusion). Long-term persistence of CCR5-modified cells suggested the
ir presence within long-lived CD4 populations\, such as T memory stem cell
s (TSCM). To investigate the impact of persistence of “HIV-resistant”
TSCM on immune homeostasis and the decay of the HIV reservoir\, we develop
ed a mathematical model of T-cell dynamics. The model follows a linear tra
nsition from the naïve to effector memory (TEM) state and includes thymic
input of naïve cells\, proliferation\, death and differentiation rates f
or naïve and memory cells. Model fits to patient data pre- and post-injec
tion and sensitivity analysis results that increased thymic output\, an in
creased TSCM proliferation rate\, a decreased central memory cell death ra
te\, and an increased central memory transition rate played an important r
ole in increasing the T-cell count and decreasing the HIV reservoir. \n\nF
inally\, using a bi-phasic decay model\, we show that purging and replacem
ent dynamics of the CD4 T-cells population post infusion account for a sig
nificant fraction of the observed decrease in the HIV reservoir. Our resul
ts indicate that homeostatic processes can control HIV persistence\, and t
hat T-cell restoration post infusion of CCR5-deleted cells leads to the de
cay of the HIV reservoir.\n\nhttps://conferences.maths.unsw.edu.au/event/2
/contributions/137/
LOCATION:University of Sydney New Law School/--102
URL:https://conferences.maths.unsw.edu.au/event/2/contributions/137/
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SUMMARY:Liver spatial heterogeneities and HBV
DTSTART;VALUE=DATE-TIME:20180710T013000Z
DTEND;VALUE=DATE-TIME:20180710T020000Z
DTSTAMP;VALUE=DATE-TIME:20240619T111707Z
UID:indico-contribution-50-138@conferences.maths.unsw.edu.au
DESCRIPTION:Speakers: Shawn Means (University of Auckland)\nThe liver is a
spatially complex and heterogeneous network of blood and bile flows coupl
ed with metabolic processing and a favoured target for infection by hepat
ic viruses. We present here a mathematical model aimed at investigating th
ese intrinsic heterogeneities and their impact on the dynamic of the Hepat
itis-B variant (HBV). Dramatic spatio-temporal scaling from individual hep
atocytes to the entire liver organ invites multi-scale approaches inspirin
g assembly of sinusoid-level 'unit models' into a whole organ representati
on. Each 'unit-model' sinusoid combines individual hepatocytes communicati
ng with blood flow in the sinus in turn connected with other 'unit-model'
sinusoids aggregated into a whole liver modelling scheme. This permits inv
estigating impacts on the whole organ of precisely distributed spatial het
erogeneities such as varying HBV uptake mechanisms (e.g.\, the sodium-taur
ochloriate cotransporter or NTCP)\, immune cell responses (e.g.\, cytolyti
c or interferon-based) and simple efficiency of HBV replication. We presen
t our results showing how heterogeneities of\, in particular\, HBV replica
tion efficiencies may be responsible for persistent chronic infections.\n\
nhttps://conferences.maths.unsw.edu.au/event/2/contributions/138/
LOCATION:University of Sydney New Law School/--102
URL:https://conferences.maths.unsw.edu.au/event/2/contributions/138/
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BEGIN:VEVENT
SUMMARY:Memory and time delays in physiological regulation
DTSTART;VALUE=DATE-TIME:20180710T003000Z
DTEND;VALUE=DATE-TIME:20180710T010000Z
DTSTAMP;VALUE=DATE-TIME:20240619T111707Z
UID:indico-contribution-50-198@conferences.maths.unsw.edu.au
DESCRIPTION:Speakers: Jacques Bélair (Université de Montréal)\nMemory t
ranslates into time delays naturally in a number of regulatory processes a
t all levels of organisation in the life sciences: transcription and trans
lation times in molecular biology\, finite axonal conduction velocities be
tween neurons\, maturation times of precursor cells in hematopoiesis and i
nfection and temporary immune periods in infectious disease propagation ar
e but a few examples of naturally occurring such delays. In many instance
s\, mathematical constructions are elaborated to avoid incorporating time
delayed arguments in the modelling equations of the system of interest. We
present\, by way of examples on two specific physiological and epidemiolo
gical systems\, the limitations of this approach and the extent to which t
hese approximations may or may not be useful or necessary for a proper und
erstanding of the modelled system.\n\nThis talk will serve as an introduct
ion to the other presentations of the Minisymposium.\n\nhttps://conference
s.maths.unsw.edu.au/event/2/contributions/198/
LOCATION:University of Sydney New Law School/--102
URL:https://conferences.maths.unsw.edu.au/event/2/contributions/198/
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SUMMARY:Models for thrombopoiesis with bifurcation analysis
DTSTART;VALUE=DATE-TIME:20180710T020000Z
DTEND;VALUE=DATE-TIME:20180710T023000Z
DTSTAMP;VALUE=DATE-TIME:20240619T111707Z
UID:indico-contribution-50-184@conferences.maths.unsw.edu.au
DESCRIPTION:Speakers: Joseph Mahaffy (San Diego State University)\nThrombo
poiesis is the process for producing platelets\, which uses a negative fee
dback to maintain homeostasis in normal individuals. However\, pathologica
l states exist where platelet concentrations in the body oscillate. An age
-structured model for thrombopoiesis was developed and fitted to clinical
data for subjects with normal and pathological platelet production. Variat
ions on this model are described to obtain more details on how this system
undergoes a Hopf bifurcation. Our study explores parameter sensitivity an
d which model features are most significant in the bifurcation to periodic
solutions. We observed that near the Hopf bifurcation there is a very rap
id transition of the stationary solution along with the change in the real
part of the leading pair of eigenvalues. The creation and analysis of the
characteristic equations from these models provide some interesting new i
deas. Certain model reductions decrease the complexity of the characterist
ic equation and allow a better understanding of the source of the Hopf bif
urcation. Our modelling efforts might improve insight into the primary pro
blems underlying the diseased state\, where levels of platelets and thromb
opoietin vary periodically.\n\nhttps://conferences.maths.unsw.edu.au/event
/2/contributions/184/
LOCATION:University of Sydney New Law School/--102
URL:https://conferences.maths.unsw.edu.au/event/2/contributions/184/
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