Aug
12
Mon
2013
Plenary Talk: Realistic modeling-new insight into the functions of the cerebellar network @ Amriteshwari Hall
Aug 12 @ 1:37 pm – 2:24 pm

egidioEgidio D’Angelo, MD, Ph.D.
Full Professor of Physiology & Director, Brain Connectivity Center, University of Pavia, Italy


Realistic modeling: new insight into the functions of the cerebellar network

Realistic modeling is an approach based on the careful reconstruction of neurons synapses starting from biological details at the molecular and cellular level. This technique, combined with the connection topologies derived from histological measurements, allows the reconstruction of precise neuronal networks. Finally, the advent of specific software platforms (PYTHON-NEURON) and of super-computers allows large-scale network simulation to be performed in reasonable time. This approach inverts the logics of older theoretical models, which anticipated an intuition on how the network might work.  In realistic modeling, network properties “emerge” from the numerous biological properties embedded into the model.

This approach is illustrated here through an outstanding application of realistic modeling to the cerebellar cortex network. The neurons (over 105) are reproduced at a high level of detail generating non-linear network effects like population oscillations and resonance, phase-reset, bursting, rebounds, short-term and long-term plasticity, spatiotemporal redistrbution of input patterns. The model is currently being used in the context of he HUMAN BRAIN PROJECT to investigate the cerebellar network function.

Correspondence should be addressed to

Dr. EgidioD’Angelo,
Laboratory of Neurophysiology
Via Forlanini 6, 27100 Pavia, Italy
Phone: 0039 (0) 382 987606
Fax: 0039 (0) 382 987527
dangelo@unipv.it

Acknowledgments

This work was supported by grants from European Union to ED (CEREBNET FP7-ITN238686, REALNET FP7-ICT270434) and by grants from the Italian Ministry of Health to ED (RF-2009-1475845).

Egidio

Aug
13
Tue
2013
Delegate Talk: A Novel Versatile Human Cell Based In Vitro High Throughput Genotoxicity Screen @ Acharya Hall
Aug 13 @ 6:50 pm – 7:00 pm
Delegate Talk: A Novel Versatile Human Cell Based In Vitro High Throughput Genotoxicity Screen @ Acharya Hall | Vallikavu | Kerala | India

Sunilkumar Sukumaran, Ayyappan Nair, Madhuri Subbiah, Gunja Gupta, Lakshmi Rajakrishna, Pradeep Savanoor Raghavendra, Subbulakshmi Karthikeyan, Salini Krishnan Unni and Ganesh Sambasivam


Genotoxicity is defined as DNA damage that leads to gene mutations which can become tumorigenic. Genotoxicity testing is important to ensure drug safety and is mandatory prior to Phase I/II clinical trials of new drugs. The results from genetic toxicology studies help to identify hazardous drugs and environmental genotoxins. Currently, among others there are four tests recommended by regulatory authorities (Ames test-bacterial, chromosome aberrations; in vitro gene mutation-eukaryotic cells and in vivo test). These assays are laborious, time consuming, require large quantities of test compounds and limited by throughput challenges. The site and mechanism of genotoxicity are not revealed by these assays and data obtained from bacterial tests might not translate the same in mammals. To address these we have developed a novel, versatile, human cell based, high throughput, reporter based genotoxicity screen (Anthem’s Genotox screen). This screen is performed on genetically engineered human cell lines that express 3 reporter genes under transcriptional control of ‘early DNA damage sensors’ (p53, p21 and GADD153). These genes are involved in DNA repair, cell cycle arrest and/or apoptosis. p21 and GADD are also known to be induced in a p53 independent manner. p53 blocks G1/S transition of cell cycle while the p53 independent DNA damage block G2/M transition. Identification of the mechanism of genotoxicity helps in rational drug designing. Additionally, the platform can be used to screen other potential genotoxins from cosmetics, food and environment. Initial validation studies of the Genotox screen was performed with over 60 compounds chosen from a variety of chemical classes. The genotoxic potential of metabolites was tested using rat liver S9 fractions. The results demonstrated a sensitivity of 86.7–92.3% and a specificity of 70–78.6% when compared with currently available in vitro genotoxicity assays. This Genotox screen would prove to be an invaluable human cell based tool to weed out potential genotoxins in various industries.