Keynote Speaker 1

Integration of Personal Genomics, Pharmacokinetics, Dietary Supplements and Cancer
Ah-Ng Tony Kong
The State University of New Jersey, USA

Wednesday, 2 December 2009
09:45 - 10:30 hrs
Breakthrough Room, Level 4, Matrix, BIOPOLIS

ABSTRACT:
The use of molecular genetics to analyze an individual's response to dietary nutrition or medicine so that optimal health outcomes can be achieved is gaining a lot of attention and is referred to personalized genomics. The response to dietary food factors is determined in part by the effective concentrations of the "bioactive" food components individually or mixed reaching the target tissues governed by pharmacokinetics and the threshold amount required to trigger a response governed by chemical-receptor/protein interactions. Hence this threshold response to food factors/drugs could vary from individual to individual depending on their genetic make ups. In this context, evolutionarily animals had been ingesting plants and plants had been producing so called "toxic" chemicals for protection, which given rise to the animal-plant warfare. This animal-plant warfare has resulted in an elaborated system of defense mechanisms evolved by animals. Animal cells including human respond to these plant phytochemicals by sensing the chemical-stress such as protein-thiol modification of the molecular targets resulting in changes of gene expressions or protein functions. Our lab has been studying several classes of dietary food factors including isothiocyanates (ITCs), polyphenols, tocopherols and polyunsaturated fatty acid (PUFA). These phytochemicals modulate gene expression such as defense enzymes GST, HO-1, GCS via Nrf2-Keap1/ARE signaling pathway. Using Nrf2-/- mice with Affymetrix microarray analyses, nuclear transcription factors/coregulators, kinases/phosphatases, cell growth/apoptosis, cell adhesion, electron transport, and ubiquitination, also require Nrf2 for the overall cellular protective effects against oxidative/carcinogenic damages. These Nrf2-/- mice are more prone to carcinogens-induced skin, colon, stomach and other cancers and more susceptible to DSS-induced colon inflammation and DSS-AOM-induced carcinogenesis. Importantly, in the skin tumors and prostate TRAMP tumors, as cancer progresses, a shut-down of Nrf2 and ARE-mediated gene expression such as GST occurred and appear to be reversed in part by mixed tocopherols, ITC and curcumin diets. Future research integrating personal genomics, nanotechnology-based targeting, imaging technology, biomarkers and pharmacodynamic response would accelerate drug discovery, patient healthcare and strategy to disease control and prevention.
This research was supported in part by Institutional Funds, RO1-CA073674, RO1-CA094828, R01-CA118947 and P30ES005022 from the National Institutes of Health (NIH).

Keynote Speaker 2

Sustainable Pharmaceutical Processing - more reliable, smarter and cleaner
Paul Sharratt
ICES, Singapore

Thursday, 3 December 2009
09:00 - 09:45 hrs
Breakthrough Room, Level 4, Matrix, BIOPOLIS

ABSTRACT:
Pharmaceutical production techniques have been a matter of much discussion in recent years from within and outside the industry. While the industry has traditionally been very innovative in its approach to product design, only recently has there been attention paid to the strategic development of manufacturing technology. There is now a realisation of the need for a step change in processing performance to increase process reliability, reduce costs, increase supply chain agility and reduce environmental impacts.

A number of interlinked themes have emerged - Process Analytical Technology, batch to continuous conversions, green chemistry and technology, supply chain analysis and process understanding and all are being actively developed by the industry, consultants, equipment suppliers and research institutes. While superficially this might be seen as the arrival of modern, efficient manufacturing (as happened over 50 years ago in the manufacture of petrochemicals, for example) the reality is that this is an immensely difficult and complex area. In API manufacture, chemistries are highly complex and often novel, while secondary processing most processes involve the preparation of highly structured products(like tablets) with very tight quality constraints.

Behind these industry challenges lie a range of science and technology challenges that are themselves difficult for the research community as they are inevitably multidisciplinary and often involve phenomena that are not well enough understood to allow quantitative prediction of behaviour. Some examples that illustrate the nature of the problems that are to be addressed are:

There are opportunities for researchers to make a big contribution to the manufacturing revolution in the pharmaceutical sector. This will require approaches that challenge some of the traditional discipline-based organisation of research; it is often difficult to promote the kind of cross-disciplinary approaches that will be required in the current structures of publically funded research.

Keynote Speaker 3

Simulating the Biomechanics of Bone
Sally Clift
Senior Lecturer in Mechanical Engineering, University of Bath, UK
& Editor-in-Chief Medical Engineering & Physics

Thursday, 3 December 2009
09:45 - 10:30 hrs
Breakthrough Room, Level 4, Matrix, BIOPOLIS

ABSTRACT:
Bone is a hierarchical material which has a complex and sophisticated response to load. Exploration of this response offers the possibility of informing future strategies for the maintenance of health and the treatment of disease.

The finite element method is a computer based approach which is very widely used. It offers the capability for prediction of the stress and strain distributions generated in anisotropic materials of three dimensional geometry. It does, however, generate an approximate rather than exact solution and therefore needs to be carefully validated. In biomechanics, this process of validation can be extremely challenging and requires careful and thoughtful formulation of clinical and experimental comparisons.

This presentation will review the state of the art in simulation of the biomechanics of bone and explore some of the challenges for the future.

Keynote Speaker 4

Systems Pharmacology in Genomic Medicine
Edison Liu
Genome Institute of Singapore

Friday, 4 December 2009
11:30 - 12:15 hrs
Breakthrough Room, Level 4, Matrix, BIOPOLIS

ABSTRACT:
Genomic medicine involves the provision of medical care that uses the power of genomic knowledge and technologies to resolve complex problems. The fundamental difference between this and older strategies in medicine research is the comprehensiveness and the precision of the analyses afforded by new genomic technologies such as in sequencing, cloning, and genotyping. The new challenge will be the assembly and management of this high volume of data with dimensional complexity. Genomic medicine therefore means computational and systems medicine as well. Systems pharmacology, as a discipline, seeks to explain cellular responses to pharmacologic challenges through the net interactions of all cellular and biochemical components within a cell or organism. Operationally, systems pharmacology requires the digitalization of biological output, the computational power to analyze comprehensive and massive datasets, and the capacity to integrate heterogeneous data into a usable knowledge format.

We will describe how genomic approaches are changing our understanding of cancer, as a model system. Our work, at the Genome Institute of Singapore, in transcriptional profiling has led to transcription factor binding site dynamics, and human variations in those binding sites. We employ a strategy of using genomic data to reconstruct systems maps of critical regulatory networks. This integrative approach permits modeling of complex interactions and allowed us to quickly uncover complex mechanisms of drug action. Coupled with the dramatic expansion of disease gene discovery in population studies, we now find that rather than a few genes, hundreds of genes may be involved in the genesis of a single complex disease. Harnessing complexity will be our next great challenge.

Keynote Speaker 5

Phenotype MicroArray Technology: A "Phenomics" Tool for Studying Cells and Optimizing BioProcesses
Barry Bochner
Biolog, Inc., Hayward, USA

Friday, 4 December 2009
12:15 - 13:00 hrs
Breakthrough Room, Level 4, Matrix, BIOPOLIS

ABSTRACT:
Phenotype MicroArrayTM (PM) Technology is a unique platform that can be used in BioProcess development projects with virtually any type of cell: bacterial, fungal, or animal. The technology allows scientists to quickly and easily culture cells under hundreds or thousands of diverse culture conditions and simultaneously examine important parameters such as in vivo pathway activities and cell productivity. A companion instrument, the OmniLog®, can monitor 5,000 culture assays at a time and provide detailed kinetics. PMs are sets of ~2,000 preloaded cell culture assays that are performed in a standard 96-well microplate format comprised of basic cellular nutrition assays for C, N, P, and S metabolism (800 tests), pH growth range and regulation of pH control (100 tests), sensitivity to NaCl and various other ions (100 tests), and sensitivity to chemical agents that disrupt various biological pathways (1,000 tests). A slightly different set is available for animal cells. With PM technology, cell lines can be quickly and easily assessed in great detail in terms of their metabolic and chemical sensitivity phenotypes. The assay platform uses proprietary colorimetric redox dye chemistries to measure cell respiration as an alternative option to measuring growth. Examples will be presented to show how information from these assays can enlighten the user on medium composition effects on cell growth, productivity, viability, stability/instability/differentiation, and other aspects important to BioProcess improvement. By assessing the value of many culture parameters, the technology helps in efficiently finding a global process optimum in terms of both growth and culture productivity.

Keynote Speaker 6

Nanostructure Processing of Advanced Biomaterials and Biosystems
Jackie Y. Ying
Institute of Bioengineering and Nanotechnology, Singapore

Friday, 4 December 2009
13:00 - 13:45 hrs
Breakthrough Room, Level 4, Matrix, BIOPOLIS

ABSTRACT:
Nanostructured materials are of interest for a variety of applications. Through controlled synthesis in reverse microemulsions, my laboratory has achieved polymeric nanoparticles for the glucose-sensitive delivery of insulin. These stimuli-responsive materials allow for the appropriate insulin delivery to diabetic patients only when their blood sugar levels are high, without the need for external blood sugar monitoring. We have also developed apatite-polymer nanocomposite particles for the sustained, zero-order delivery of protein therapeutics. By adsorbing valuable bone morphogenetic proteins on carbonated apatite nanocrystals that are then encapsulated within biodegradable polymeric microparticles, we are able to achieve controlled release of this growth factor for the bone healing process over an extended period of time.

In addition, nanostructure processing has been employed in artificial implant and tissue engineering applications. For example, nanocomposite processing has been applied to obtain orthopedic implants and bone scaffolds with superior mechanical strength and bioactivity. By combining microfabrication and nanotechnology, we have also created various microstructures in kidney-specific dimensions and shapes. These structures can be used as bioartificial renal assist microdevices, and may serve as three-dimensional templates for tissue engineering.