Applied Sciences > Medicine > DG CY2020 8157 1

Research Title Anti-Infective and Anticancer Drug Candidates from Marine Microorganisms, Sponges and Other Microorganisms: Discovery and Development (Year 1 of 3)
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Research Duration Start:
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1 September 2019
31 August 2022
Research Location UPD-MSI
Research Description The DDHP-Marine Component Program seeks a second phase that will build on the accomplishments of the first phase to further advance marine drug discovery efforts in the country. In particular, the program will pursue further characterization and development of promising compounds discovered in Phase 1 and further develop the program's capability and infrastructure to undertake more efficient, effective, productive, and sustained drug discovery and development campaigns. By pursuing these goals, the program will be addressing the major challenges that typically hinder if not block progress in drug discovery and development programs. Among these is the fact, well known in the industry, that the number of compounds available for screening is a crucial limiting factor. The implication is that although the projects have already identified a number of promising compounds and will pursue their development, the chance of these compounds to move to clinical trials is statistically low as historically the progression of compounds through the drug discovery pipeline is characterized by very high attrition rates. Being a game of numbers, it is imperative for a drug discovery pipeline that a sufficiently large pool of novel compounds is available for screening. The high marine biodiversity available to researchers is a big advantage, but acquisition of compounds from these resources will need to be efficient and scaling up will be a necessity. The proposed program will deploy innovative solutions to this program. Developing an effective and efficient drug discovery enterprise is another important challenge. As a process, drug discovery is similar to other enterprise-scale, production-oriented operations: it works as a value chain. The creation of value is distributed over the entre chain, and a weak link can compromise the productivity of the entire chain, and a weak link can compromise the productivity of the entire enterprise. Value chains are modeled as systems composed of hierarchical subsystems. Subsystems are not just different from each other, they in fact represent distinct capabilities in the enterprise and specialize in efficiently delivering the required intermediates in the process. A productive and efficient value chain results from optimal operation not just of the component that produce the final product but of all its components. Thus, the program will further develop and strengthen its entire core value chain by ensuring that sub-systems needed for key processes are in place, and that the distinct capabilities required to effectively implement each stage of the drug discovery value chain are sufficiently developed.
Research Objectives anti-infective and/or anticancer compounds from Philippine marine sponges, other marine macroorganisms and their associated microorganisms. Specifically, it aims: 1). to improve culture techniques of renieramycinproducing Philippine blue sponge; 2). to generate extracts and fractions with confirmed biosctivity and selectivity, and characterized chemistry; 3). to determine the in vivo activity of the priority compounds in a mouse model for breast cancer; 4). to establish ADMET properties of priority compounds; 5). to determine the structure of purified compound(s) using NMR and MS and establish their potency; a. fractionate priority extracts and fractions using various chromatographic techniques; b. determine the structure of purified compound(s) using NMR and MS; and c. assess the potency of the purified compounds. 6). to produce bioactive compounds from microorganisms using bioreactors (scaled-up fermentation); 7). to develop prototype genomics-driven microbial production systems for bioactive bacterial compounds. a. improve depth-of-coverage and assembly quality of metagenomes/genomes from priority Phase 1 sponges and bacterial isolates to enable assembly of full/complete biosynthetic gene clusters necessary for their identification and for analysis of their (primary) structures; b. develop genetic techniques for activating expression of genes encoding secondary metabolites in atleast 1 priority bacterial isolate; c. undertake integrated bioinformatic analysis of genomic/metagenomic and metabolomic data to enable mapping of biosynthetic gene clusters to metabolome components and hence identification of biosynthetic gene clusters with potential products in the metabolome, inference of the structural characteristics of their predicted compounds, validation of the production of compounds using metabolomic data, and selection of gene cluster candidates for expression; d. develop a production system (i.e. native producer or heterologous host together with the culture protocol) for expressing biosynthetic gene clusters and associated metabolomics-based validation techniques for production of target compounds; e. produce the predicted compounds of at least 2 priority biosynthetic gene clusters using the production system(s); f. compare the two (screening-based and genomic/genetic-based) modes of discovery/production-based on key production parameters (including cost); and g. set up and maintain a central DDHPMC data warehouse.
Research Beneficiary(ies) 1) Medical benefits to patients; 2) Professional and economic benefits to medical doctors and health workers, hospitals and health clinics; 3) Economic benefits to Philippine Government (DOST), pharmaceutical companies, and entrepreneurs; 4) Academic institutions and researchers; 5) Local communities
Research Accoplishments [CY 2019] 1) At least 6 ISI publications Oral and poster presentations across international and local conferences; 2) At least one patent on compound production and/or application; 3) Chemical library of extracts, fractions and pure compounds; 4) Microbial library; 5) Data management system; 6) At least 1.4 kg of sponge biomass/year; 7) At least 5 mg of priority compound/year; 8) At least 1 pre-clinical lead; 9) Prototype production systems for bioactive bacterial compounds; 10) Medium scale open-sea sponge mariculture; 11) Recombinant expression setup
Total Research Cost ₱1,416,622.26
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UPD-MSI


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Code DG CY2020 8157 1
KRA Code
Priority Thrust DOST
R&D


Sector Applied Sciences
Actual Sector Medical science
Related sectors Marine Biology
Entry revision: February 2021