|Lead Investigators||Jianzhu Chen, Peter Preiser|
|MIT Investigators||Jianshu Cao, Ming Dao, Peter Dedon|
|Singapore Co-Investigators||Chwee Teck Lim|
Eradication of malaria is the long term goal of the global research effort studying this globally important infectious disease. Key prerequisites for a successful campaign are highly sensitive, cheap and reliable diagnostic tools, a panel of effective drugs as well as a vaccine that is capable to significantly reduce transmission in malaria endemic countries. To date there are challenges and limitations in relation to all these. The malaria research effort at the SMART Infectious disease IRG aims to develop novel approaches that combine state of the art technologies in biology and engineering to provide new solutions. The main areas currently investigated are:
1. Relationship between the biomechanical properties of the parasite infected erythrocyte and how this relates to pathology and disease progression.
A major cause of malaria pathology is the result of the extensive modification of the infected RBC membrane by P. falciparum, resulting in increased membrane rigidity and the propensity for infected RBCs to adhere to the endothelial lining of blood vessels in the microcirculation. These altered rheological and cytoadherence properties of parasite-infected RBCs contribute significantly to malaria pathophysiology, resulting in life-threatening complications such as cerebral and placental damage. To address these challenges, the Malaria Program will elucidate the role of parasite-altered mechanical properties of infected RBCs in disease pathogenesis by examining the molecular basis of cell adhesion and how it contributes to disease pathology, including sequestration in the deep tissues and clearance in the spleen. The findings obtained here can provide new solutions for diagnostic and clinical disease management.
2. Identification of new targets for the development of an effective vaccine.
The long-term cost-effective control of malaria requires development of malaria vaccines. However, malaria vaccine development is hampered by our lack of clear understanding of protective immune responses and lack of malaria antigens that can be used to induce the protective immune responses. The major long-term goal of the Malaria Program is to overcome these two obstacles so as to identify malaria antigens that can be used to induce protective immune responses.
3. Drug resistance to available malaria drugs is a key challenge due to the rapid development of drug resistance.
Translational control of protein expression used by the parasite may provide a new avenue to identify new drug targets and develop new drugs. Using a combination of molecular biology as well as high throughput omic approaches has shown that unique tRNA modifications may be one strategy employed by the malaria parasite to regulate expression. The process and its suitability to as a drug target a currently being investigated.