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Finding and validating non-conventional antimicrobial agents from natural products and through chemical synthesis
Finding and validating non-conventional antimicrobial agents from natural products and through chemical synthesis
We use genomics and proteomics data to mine for potential microbial moieties that could be investigated as novel therapeutic targets. Through genetic manipulation, we construct isogenic mutants in the genes encoding those moieties and complement them. Then, this set of strains (the wild-type, the mutant, and the complemented mutant) is scrutinized in a series of experiments both in vitro and in vivo to validate if they this moiety is indeed involved in the virulence of the pathogen understudy. After validation, libraries of natural and synthetic compounds are screened first in silico then in in vitro to determine if we can identify potential molecules that can interact with the identified microbial moiety to interfere with its role in causing infection in the host. Promising hits are then further characterized, tested, and modified to enhance their bio-activity. Our work in this area is focused towards the most notorious pathogen, Acinetobacter baumannii, which is showing increasing resistance to almost all the available antimicrobials.
We use genomics and proteomics data to mine for potential microbial moieties that could be investigated as novel therapeutic targets. Through genetic manipulation, we construct isogenic mutants in the genes encoding those moieties and complement them. Then, this set of strains (the wild-type, the mutant, and the complemented mutant) is scrutinized in a series of experiments both in vitro and in vivo to validate if they this moiety is indeed involved in the virulence of the pathogen understudy. After validation, libraries of natural and synthetic compounds are screened first in silico then in in vitro to determine if we can identify potential molecules that can interact with the identified microbial moiety to interfere with its role in causing infection in the host. Promising hits are then further characterized, tested, and modified to enhance their bio-activity. Our work in this area is focused towards the most notorious pathogen, Acinetobacter baumannii, which is showing increasing resistance to almost all the available antimicrobials.
Studying the role of stress proteins in bacterial physiology and virulence
Studying the role of stress proteins in bacterial physiology and virulence
We are interested in a group of bacterial proteins that are induced upon the bacterial exposure to different stressors similar to those which are encountered within the host environment. At first we evaluate the role of these proteins in the physiology as well as the virulence of the pathogen by constructing and testing isogenic mutants in well established animal models of infection. Then we study the conditions under which the genes encoding these proteins are induced and how they are regulated. Obtaining a clear picture of the genetic regulation of stress proteins paves the road for establishing big screens to identify inhibitors of such systems. Libraries of small chemical compounds either of synthetic or natural origins are attractive tools to identify molecules that can serve as nuclei for the development of new therapeutics. This kind of therapeutics is urgently needed due to the progressive increase in drug resistance.
We are interested in a group of bacterial proteins that are induced upon the bacterial exposure to different stressors similar to those which are encountered within the host environment. At first we evaluate the role of these proteins in the physiology as well as the virulence of the pathogen by constructing and testing isogenic mutants in well established animal models of infection. Then we study the conditions under which the genes encoding these proteins are induced and how they are regulated. Obtaining a clear picture of the genetic regulation of stress proteins paves the road for establishing big screens to identify inhibitors of such systems. Libraries of small chemical compounds either of synthetic or natural origins are attractive tools to identify molecules that can serve as nuclei for the development of new therapeutics. This kind of therapeutics is urgently needed due to the progressive increase in drug resistance.
The development of diagnostic kits and useful biotechnological reagents
The development of diagnostic kits and useful biotechnological reagents
Making good use of the available numerous bioinformatic and biotechnological resources, we are designing, producing, and testing several reagents. These reagents can be incorporated into the production of accurate, rapid, and low cost diagnostic kits for a group of emerging and re-emerging infectious agents. The need for such kits is critical especially in developing countries like Egypt which has tight economic resources and faces the spread of clinically challenging infections. Other reagents produced by our group have biotechnological applications in the molecular biology, medical, and environmental fields.
Making good use of the available numerous bioinformatic and biotechnological resources, we are designing, producing, and testing several reagents. These reagents can be incorporated into the production of accurate, rapid, and low cost diagnostic kits for a group of emerging and re-emerging infectious agents. The need for such kits is critical especially in developing countries like Egypt which has tight economic resources and faces the spread of clinically challenging infections. Other reagents produced by our group have biotechnological applications in the molecular biology, medical, and environmental fields.
Designing and evaluating good vaccine candidates
Designing and evaluating good vaccine candidates
With the increasing threats of treatment failures of many infectious diseases, finding a good vaccine that would prevent the initial infection is an attractive alternative. Making use of the tremendous advances in `the immune-bioinformatics field, we use in-silico analyses tools to extensively scrutinize microbial moieties for the candidacy of being a vaccine component. High scoring candidates are evaluated in vivo using recombinant DNA technologies to clone, express, and purify bacterial targets that are then tested in well established animal models. Our focus is on some of the bacterial pathogens that are affecting large populations worldwide and in particular in the developing world. At the same time those pathogens are showing alarming trends in the clinic and the community of wide spread antimicrobial resistance.
With the increasing threats of treatment failures of many infectious diseases, finding a good vaccine that would prevent the initial infection is an attractive alternative. Making use of the tremendous advances in `the immune-bioinformatics field, we use in-silico analyses tools to extensively scrutinize microbial moieties for the candidacy of being a vaccine component. High scoring candidates are evaluated in vivo using recombinant DNA technologies to clone, express, and purify bacterial targets that are then tested in well established animal models. Our focus is on some of the bacterial pathogens that are affecting large populations worldwide and in particular in the developing world. At the same time those pathogens are showing alarming trends in the clinic and the community of wide spread antimicrobial resistance.
Effect of infectious agents and pharmacogenomics on therapeutic outcomes
Effect of infectious agents and pharmacogenomics on therapeutic outcomes
The presence of an infectious agent in the human body elicits many changes and stimuli. When this is combined with a disease linked to a certain genetic polymorphic allele this can lead to either a positive or a negative effect on the outcome of the therapy administered for the treatment of such disease. We are currently working on two projects related to this theme namely; (i) the effect of bacterial loads and genetic polymorphisms on the treatment of chronic obstructive pulmonary disease (COPD), (ii) the effect of Hepatitis C virus (HCV) infection and genetic polymorphism on the treatment of childhood acute lymphoblastic leukemia (ALL). Both projects are carried out in collaboration with Dr. Nirmeen A. Sabry in the Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmacy, Cairo University.
The presence of an infectious agent in the human body elicits many changes and stimuli. When this is combined with a disease linked to a certain genetic polymorphic allele this can lead to either a positive or a negative effect on the outcome of the therapy administered for the treatment of such disease. We are currently working on two projects related to this theme namely; (i) the effect of bacterial loads and genetic polymorphisms on the treatment of chronic obstructive pulmonary disease (COPD), (ii) the effect of Hepatitis C virus (HCV) infection and genetic polymorphism on the treatment of childhood acute lymphoblastic leukemia (ALL). Both projects are carried out in collaboration with Dr. Nirmeen A. Sabry in the Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmacy, Cairo University.
Our work focuses on following pathogens:
Our work focuses on following pathogens:
Gram negative bacteria : Acinetobacter baumannii and Moraxella catarrhalis
Gram negative bacteria : Acinetobacter baumannii and Moraxella catarrhalis
Gram positive bacteria: Staphylococcus aureus, Staphylococcus lugdunensis, and Staphylococcus epidermidis
Gram positive bacteria: Staphylococcus aureus, Staphylococcus lugdunensis, and Staphylococcus epidermidis
Viruses: Hepatitis B virus, and Hepatitis C virus
Viruses: Hepatitis B virus, and Hepatitis C virus
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