School of Biological Sciences

Reg. No. 200604393R

Research Theme: Drug discovery, Isolation and Characterization of Natural Products

Research Project Title: Discovery of Druggable Biologics from Medicinal Plants
Principal Investigator/Supervisor: Prof James P Tam
Co-supervisor/ Collaborator(s) (if any):
Project Description
Background

Biologics are peptides and proteins with therapeutic potentials. They have MW considerably >500
Da and large footprint, which confers them high specificity and low toxicity. Currently, biologics
represent the largest group of therapeutics, adjuvants and synthetic vaccines under different phases
of clinical trials. Despite a long history of prevalent usage in plant products and herbal concoctions,
few plant biologics are known. Past investigations of the active principles in herbal medicine have
entirely focused on small molecules and missed the full landscape of bioactive biologics. Indeed, a
data base of >20,000 plant-derived molecules with known or undetermined medicinal values are
small molecules or non-peptide compounds. A contributing factor to this neglect is the intrinsic
instability of peptides and proteins against heat during decoction preparations or their susceptibility
to enzymatic and acidic hydrolysis during ingestion. In addition, few biologics are orally bioavailable
through gut absorption or uptake, irrespective of their source of origin. However, recent literature
precedents suggest otherwise.

Cumulative evidence shows that several classes of cysteine-rich peptides (CRPs) in plants such as
defensins, thionins, leginsulins, knottins and cyclotides are highly stable. They are very common in
plants and genomic analysis of two model plants Arabidopsis thaliana and Oryza sativa (rice) reveal a
surprise abundance of genes encoding for CRPs which account for up to 2-3 % of the gene repertoire
of each model species. Although the primary sequences, biochemical properties and functions may
differ greatly, CRPs possess multiple disulfide bridges that cross brace their structures conferring
them thermal, chemical and enzymatic stability. In addition, most possess an amphipathic structure
which may promote their absorption through gut. These characteristics make CRPs the likely active
principles in herbal medicine.

Proposed work

The major aims of this project are: (1) Discovery of novel biologics from medicinal plants. (2)
Pharmacological profiling of novel biologics base on their traditional usages in folk medicine. The
proposed study may provide leads compound for drug development and aid in quantitative profiling
of active ingredients in commercial viable medicinal herbs.
Supervisor contact:
If you have questions regarding this project, please email the Principal Investigator:
jptam@ntu.edu.sg
SBS contact and how to apply:
Associate Chair-Biological Sciences (Graduate Studies) : AC-SBS-GS@ntu.edu.sg
Please apply at the following: http://admissions.ntu.edu.sg/graduate/R-Programs/R-
WhenYouApply/Pages/R-ApplyOnline.aspx

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