Project 1. Structure-activity relationship (SAR) studies of host defence peptides with immunomodulatory properties
Cationic host defense peptides (HDPs) are regarded as one of the most promising alternative infectious disease therapies. HDPs, formerly known as antimicrobial peptides, are evolutionary conserved, hydrophobic and amphipathic short (<50 amino acids) cationic molecules with a net charge of +2 to +9. HDPs are ubiquitous defence biomolecules in nature; they are produced in virtually all organisms ranging from plants and insects to humans, and comprise an integral component of innate defences against infections.

Project 2: Investigations of interactions between host defence peptides and mycobacteria in vitro and in vivo.
Worldwide Tuberculosis (TB), caused by Mycobacterium tuberculosis (MT), is a leading infectious disease causing significant morbidity and death. Currently at least one third of the world population are infected with MT and this number might increase in coming years due to emergence of drug resistant strains and difference in protection efficiency (~80%) among the individuals obtaining the BCG vaccine. MT deserves special attention, not only for being a significant pathogen, but also for absence of classical bacterial virulence factors and most important, its unique cell wall architecture, which is not found in other prokaryotes.
Israel et.al proposed that the innate immune response could be a significant factor in the natural resistance against mycobacterial infections and induction of long term control. Strangely, even though innate immunity is the first defence mechanism that encounters MT, the interaction of MT with innate immunity has not been investigated fully.

Project plan  3:designing novel host defence peptides with antimicrobial and wound healing properties

Wounds are common, inescapable and integral aspect of human life.  In course of time, minor wounds are healed with scars, however some wounds, especially those caused by burns or bacterial infection are usually lethal and account for prime cause of death. Usually in case of burn/chronic wounds, the problem is multi dimensional, i.e. you have a breach in the innate immunity, sepsis due infection and over activation of the immune system leading to multiorgan failure. Despite some improvements, in the early wound care, still sepsis and systemic inflammatory response remain major causes of morbidity and mortality in patients. The current method of treatment involves using antibiotics combined with immune suppressors, which are not efficient totally. Antibiotic therapy extensive application has provided selective pressure for the development of multidrug resistant microbes, thus creating situations in which these therapies fail.  On the other hand, immune suppressors work in a blind fashion, they block the pathways so that a cascade is not activated. This non-specific action creates a confusion state, which leads to complications in treatment or death, as immune components are linked with one other and are not independent of each other. Very recently it has been confirmed that, in case of burn wounds, death of the individual occur not because of the absence of the skin, but due to loss of antimicrobial peptides and innate immunity coordination with adaptive system.

Project plan  4: Identification and use of novel microbial proteolytic enzymes as drugs to cure auto immune disease and post-transplantation complications
The most important part of this research, in addition to gaining an understanding of microbial modes of infection, is the direct application of technology developed into human therapeutics for the prophylaxis and treatment of infectious diseases. The research field of pathogen–derived immunomodulatory (IM) molecules is rapidly developing and several IM’s have been identified as potential immune therapeutics. Discovery of new immune diseases conditions (i.e autoimmune, transplant, inflammatory related) has draw the attention our attention towards microbial enzymes, especially those that are pathogen associated, as novel drug molecules. Interestingly, the study of microbial enzymes is of dual use; firstly it help us to understand how microbes avoid the detection of  sophisticated and advanced host immune system, thus paving the way to develop new drugs which target this vital routine and kill the microbes. Secondly, they provide us with molecules by which we can modulate our own immune system in the way we want, especially in the case of organ transplantation or autoimmune disorders.
Most pathogenic microbes produce virulence factors, which either specifically cause disease or influence the ability of the organism to colonize or persist within the host. For example, Staphylococcus aureus useshyaluronidase, protease, coagulase, lipases and enterotoxins as virulence factors where as Streptococcus pyogenes uses M protein, streptokinase, streptodornase, hyaluronidase, spenceronic, dorsettonic, and streptolysins. It is interesting to note that no two organisms use identical set of virulence factor or defense mechanisms for their establishment of disease. Even though the molecules used might be different, most of them belong to proteins class. In general, they use proteins/enzymes as defense mechanism to fight back against the host immune system and establish themselves in the host.

Project 5:  Cloning and expressing novel host defense peptides in yeast system for large scale production.