Promoting Biotechnology Research and Development in Sabah
SaBC is collaborating with Natural Products Chemistry Laboratory, Institute for Tropical Biology and Conservation, Universiti Malaysia Sabah in a project entitled Unlocking Sabah’s marine and terrestrial biotechnological potential. The project that will start in May 2012 and ends in December 2013 is funded by the State Government under the 2nd roll plan of the 10th Malaysian Plan with an allocation amounting RM1.58million.
- Production of chemical compounds of selected Sabah’s marine and terrestrial biological resources.
- Establishment of database of specimen, extract and chemical profiles of Sabah’s biological resources.
Benefit to Sabah, Malaysia
- Support efforts in building up the State's economic competitiveness through modern biotechnology.
- As a long term strategy in building up Sabah's technological capability in biotechnology.
- Support the State biodiversity conservation efforts by creating awareness to the people (especially Sabahan) on the value of its biological resources (through biotechnology) to the mankind.
Future Activities – 2013 to 2018
SaBC main goal in promoting biotechnology R&D is to support the creation of biotechnology industry in Sabah. Therefore, the activities will not only be confined to screening potential biological resources and producing chemical compounds but will proceed up to cell-based analysis, pharmacogenomics and pre-clinical trials research. In the meantime, Pharmaceuticals/nutraceuticals companies will be sought to bring such biotech products to the market. These activities will be strategically performed by establishing collaboration with partners that have been pre-identified by SaBC.
Biotechnology in the Pipeline:
CELL-BASED SCREENING OF SABAH’S NATURAL PRODUCTS
The State Government of Sabah through Sabah Biodiversity Centre (SaBC) has signed an agreement with AvantiCell AsiaPacific Sdn. Bhd. (AvantiCell AP) on 24th November 2014 in Kota Kinabalu for cell-based screening of Sabah’s natural products. This project is a continuation of the SaBC and Universiti Malaysia Sabah project entitle “Unlocking Sabah’s Marine and Terrestrial Biotechnological Potential”. This project is expected to be completed in the middle of 2016.
AvantiCell AP a wholly owned subsidiary of AvantiCell Science Ltd., Scotland will screen pure selected compound of Sabah’s natural products and herbal extracts for their therapeutic potential across a panel of disease indications such as inflammation, cancer, diabetes and hypertension. Pure compounds will be tested for their therapeutic potential in the treatment of inflammation, breast cancer and hypertension. Herbal extracts will be tested for activity against diabetes type II, breast cancer and inflammation. In addition, all materials will be evaluated in terms of liver toxicity. SaBC has selected to have a total of 400 samples analysed, in which 100 are pure compounds and 300 are herbal extracts. Variation from these numbers, or the selection of an alternative therapeutic target, may require compensatory adjustments to be made to the overall timeline or to the total number of samples analysed so as to adhere to the agreed budget.
The project will use a range of cellular and molecular methods to screen for therapeutic activity in the SaBC library of pure chemical compounds and herbal extracts. Each disease indication requires, in addition to the use of a specific cell type, the application of a specific analytical tool in order to measure a cellular activity affected by the disease (and potentially reversed by the presence of a bioactive chemical compound). The relevant cellular processes relevant to each disease target are as follows:
Cancer: The project will evaluate anti-cancer activity as ability to prevent or reduce cancer cell growth in culture. The selected cancer target shall be breast cancer. Human primary breast cancer cells used in this analysis are from a primary lobular carcinoma with comedo-structures removed at tumour stage pT1. Isolated cell marker status is: positive for oestrogen receptor, EpCAM, CD44, CD24, CD66, Her2, negative for CD133.
In pure compounds already partially evaluated for anti-cancer activity, potential therapeutic effect shall be measured as ability to induce cancer cell death (apoptosis) in primary human breast cancer cells. Apoptosis shall be measured as induction of executor caspase 3/7 by means of a validated fluorescence-based assay. Assays shall be calibrated using a positive control (staurosporine) and enzyme standards. In herbal extracts not yet studied for anti-cancer potential, anti-cancer activity shall be measured as prevention of or reduction in cancer cell growth in culture.
Inflammation: The project will induce inflammation in human primary monocyte populations characterised as cell marker CD14-positive (CD14+). The anti-inflammatory action of candidate therapeutics shall be measured as inhibition of inflammatory response measured as reduction in the levels of pro-inflammatory cytokines. Screening activity shall make measure inflammation and anti-inflammatory action as increase and reduction in cytokine interleukin-1β, measured by ELISA. Study of mechanism of action shall measure a panel of inflammatory cytokines using immunobead-based multiplexed analysis (BD Instruments Ltd), employing flow cytometry of medium conditioned by monocyte cells to discriminate between different bead sizes and therefore different cytokines. The cytokines selected for this multiplexed analysis shall be IL-1β, IL-6, IL-10, TNF-a. Analysis shall be calibrated by means of pure cytokine standards.
Hypertension: The project will deliver analysis of anti-hypertension activity using a cell-based system incorporating human primary vascular endothelial cells (“HUVEC”). Therapeutic potential will be assessed by measuring change in the level of angiotensin converting enzyme (ACE) due to the presence of each candidate pure compound. ACE shall be measured by ELISA in cell supernatants prepared from treated and untreated cells. Off-target effect of candidate therapeutics shall be assessed by testing against an unstimulated endothelial cell population.
Type II diabetes: The project describes analysis of anti-diabetic activity using a cell-based system incorporating human adipocytes obtained by differentiation from primary pre-adipocyte precursor cells. Therapeutic potential will be assessed by measuring glucose uptake in the presence and absence of each candidate plant extract. Glucose uptake shall be measured as uptake of a fluorescent glucose analogue by cells in culture.
Hepatotoxicity: Materials with therapeutic potential in disease treatment or prevention may have off-target adverse effect in other tissues. The potential of pure compounds and herbal extracts to cause liver damage is an important indicator of potential toxicity, and shall be measured using human liver cells which exhibit liver function in culture. Cytotoxic cell damage is measured by the leakage of intracellular cytosolic dehydrogenase enzymes from cells following damage to the outer cell membrane. These cytosolic enzymes are measured in the cell culture medium by a sensitive fluorescent method.