- Ph.D. candidate, Department of Medicine, McGill University, Montreal, Canada (1991-1998)
- M.Sc. Honors Department of Biochemistry, Charles University, Prague, Czech Republic (1985-1990)
- Assistant Professor, School of Biological Sciences, Nanyang Technolgical University, Singapore. (2004-present)
- Postgraduate researcher, Dept. of Biochemistry, University of California San Francisco, CA, USA. (2000-2004)
The main focus of ZB-lab is to uncover unique molecular features that define the lifestyle of human malaria parasites using functional genomics and proteomics and other leading edge systems biology techniques. Our main goal is to exploit these mechanisms for development of new malaria intervention strategies that include new drugs and vaccines as well as deriving better diagnostic tools for treatment, prevention and diagnosis.
Together with HIV and tuberculosis, malaria is presently one of the most lethal infectious diseases on the planet. It is caused by parasitic microorganisms of genus Plasmodium amongst which P. falciparum and P. vivax have by far the highest impact on the human population. Every year, malaria affects about 300 million and kills at least 2 million people, causing huge economic setbacks for many countries of the tropical and subtropical world. Moreover, rapidly increasing numbers of drug resistant malaria cases and the absence of an effective vaccine create a major concern for the future.
mRNA and protein expression throughout the 48 hour P. falciparum intraerythrocytic developmental cycle1
One of our major interests in this lab is the transcriptional and posttranscriptional regulation of gene expression during the Plasmodium life cycle. Our previous work contributed to the understanding of gene expression regulation during the Plasmodium life cycle 1-4, and it is now clear that essentially every gene in the genome is tightly regulated such that it is activated precisely when needed during the parasite development. In one of our recent projects, we established that histone modifications (acetylations and methylations) play a major role in the life cycle-dependent transcriptional regulation, and discovered that one class of the effector enzymes (histone deacetylases, HDACs) is indispensable for the Plasmodium life cycle progression5-7. Together with our collaborators, we are pursuing molecular mechanisms that control these processes including epigenetic regulation and transcription factors as well as protein expression and posttranslational modifications8-13.
We are also exploring gene expression in natural malaria infections in order to understand gene expression patterns that underline physiological states of Plasmodium in response to external conditions such as drug pressure or host environment14-16. These physiological states reflect phenotypic variability of infection that determines severity and outcome of the disease, symptom profile, transmission efficiency and other important parameters of malaria. Presently, we participate in the global malaria initiative to track the resistance of malaria to artemisinin, the main chemotherapeutic again for malaria treatment (TRAC study). First cases of artemisinin resistance have been detected in several spots in Southeast Asia including the Thai-Cambodia and Thai-Myanmar borders. Here, we uncovered that the resistant parasites are characterized by shifts in global transcriptional profile that allows the parasite to escape the drug15. Presently, we are collaborating with numerous research groups in Southeast Asia, Oceania, and Africa to study various features of malaria epidemiology and molecular aspects using methods of functional genomics and proteomics.
Blueprint of the protein network implicated in merozoite invasion. (a) Subnetwork associated with merozoite invasion process with a total of 2,417 links (purple lines) with 418 proteins involved in parasite invasion. (b) Schematic representation of an invasive merozoite.
Generating large transcriptomics and proteomics data from both in vitro and in vivo studies allows us use approaches of systems (integrative) biology to assemble protein interactomes and thus reconstruct the metabolic and cellular functional network of the malaria parasites17. We use advance bioinformatics and mathematic methods to derive functional annotations for the large sum of the Plasmodium proteins that lack any functional information based on their primary sequence.