Download INTERDISZCIPLINÁRIS DOKTORI ISKOLA

POSTGRADUATE SCHOOL OF INTERDISCIPLINARY SCIENCES
(Health Sciences, Theoretical Medicine, Biology)
The School offers a PhD programme to graduate students and focuses its
research and training on the role of health threatening microorganisms and dangerous
environmental effects. Both epidemiologic and experimental studies are necessary to
identify physical and chemical effects that cause health problems. The courses of the
Medical Microbiology and Preventive Medicine programs are combined in this PhD
School and offer a wide variety of research.
Microbes in the environment and those living in higher organisms are among the
major factors affecting the health and welfare of mankind. Due to chemotherapeutics,
antibiotics, and effective vaccination strategies, dreadful infectious diseases have
disappeared or considerably lost their significance. However, it has been recognized that
their place has not remained unoccupied. The eliminated microbes have been replaced
by previously unknown viruses, bacteria or other pathogens. The contribution of
bacteria and viruses has been increasingly recognized in the pathomechanisms of
diseases of unknown aetiology. As a consequence of the extended use of antibiotics,
polyresistant strains have been selected. New antigenic mutants have emerged under the
pressure of host immune responses. The classical routes of microbial spreading have
been replaced by transmission connected with hospitalization, drug abuse and
occupational hazards. The results of campaigns to eliminate various infections are still
dependent on the hygiene, geographical location and standard of living of a given
population.
Recent progress in science and application of the results of molecular biology
have opened up new prospects in the clarification of the etiology and the pathomechanisms of infectious diseases and in the development of new approaches to the
therapy and prevention. The infection by pathogens induces diverse sets of defensive
responses from the host immune system. Therefore, in this program we are dealing with
the host response, with the innate, and with the adaptive defenses. Cytokines are the
major orchestrators of host defense processes and, as such, are involved in respones to
exogenous and endogenous insults, repair and restoration of homeostasis. Cytokines
however mediate not only host response to invading organisms, tumors, trauma, but
they are produced in response to many nonpathogenic stimulants presents in our
conventional environment. Consequently, the burgeoning field of cytokine research is
unique and interdisciplinary.
Cytokines are critical for the immunological control of infections. Paradoxically
cytokines can be responsible for the development of symptoms of several infectious
diseases. In these cases the host responses to a pathogenic organism, rather than the
microbe itself may induce injury to host tissues. Prolonged exposure to high
concentration of cytokines and other components of the immuno-inflammatory cascade
may contribute to the development of multiple organ failure.
The specific aim of the program is to determine the role of cytokine activation in
diseases where the activation of the cytokine cascade by microorganisms or other agents
or both can be expected. The effects of cytokines on cell growth and differentiation, the
molecular mechanism of their interaction, and the roles of gene expression and
transcription factors will be studied.
The subprogramme investigates the pathogen-host relationship at the molecular
level, focusing on: 1. characteristics of bacteria and viruses that cause chronic diseases,
e.g., cardiovascular diseases such as atherosclerosis and tuberculosis; 2. immune
mechanisms leading to the elimination of bacteria and viruses or to disease of the host;
3. mechanisms and consequences of viral and bacterial latency with reactivations, which
often develop following an acute infection; and 4. the relationship between certain
intracellular bacterial and viral infections and their potential importance in the
pathomechanism of chronic diseases.
The process of infection can be characterized as a race between the pathogen and
the host. Modern-day microbial genetics has opened new frontiers to study
pathogenicity of bacteria and viruses.
We can observe three trends in the development of antimicrobial chemotherapy.
First: to isolate new natural, mainly microbial substances. Second: the preparation of
synthetic compounds with chemotherapeutic activity or the chemical modification of
natural products. Third: alternative interventions not inhibiting bacterial growth directly,
but antimicrobial in respect of the final outcome by inhibiting antibiotic resistance
mechanisms or adsorbtion of bacteria on the target cells.
Further aims are related to antibacterial, antitumour and antiviral chemotherapy,
i.e. the evaluation of combined chemotherapy with new constituents or combinations
which have not been tested so far, e.g. compounds inducing differentiation, apoptosis or
modifying the resistance of microbes.
Pathogenic organism carries a number of virulence genes with host origin.
Products of these genes interfere with the development of the adequate immune
response, inhibit inflammation, induce oncogenic transformation of cells, etc. Within
the framework of Genomics of pathogenic organisms we want to explore the genomes
of viruses and bacteria to find resistance genes, virulence genes and potential targets of
anti-pathogenic drugs and therapies. We also want to study those human (mammalian)
genes and sequences, which might be important as sensitivity/resistance factors in cases
of certain infectious diseases.
The etiological role of health damage of environmental origin and adverse
features of lifestyle in population diseases is evidenced by results of various
international and Hungarian epidemiological studies. Prevention of such effects by
reduction or elimination of harmful exposure would greatly contribute to the
improvement of the health status of the population in question.
Experimental studies are essential in the investigation of ill effects of natural
origin. The mechanism of action of harmful physical or chemical factors, or their
combinations, can only be achieved by animal experimentation modelling human
exposure. In the course of the experimental work, one of the goals may be the
elaboration of biomarkers, early indicators of harmful effects with potential application
in human toxicology.
The complex investigations outlined above can serve as the basis for risk
assessment and management programs, capable of reducing or eliminating harmful
effects of environmental chemical or physical factors.
Evidence Based Medicine. The availability of EBM, is an everday practice in
developed countries. It is a real interdisciplinary science, which synthetize the results of
basic and clinical sciences, epidemiology, biostatistic.
The aim of the course is the introduction of the evidence based medicine into the
clinical practice, and to teach the possibilities Research topics.
RESEARCH ACTIVITIES
Medical Microbiology, Antimicrobial Immunity
A: Role of Cytokine in Infectious and Non-Microbial Diseases
Research topics:
1. Study of cytokine gene polymorphism in septic diseases
2. The role of cytokine production in Helicobacter pylori infections
3. Cytokine gene polymorphisms
4. The role of pattern recognition receptors in cytokine induction
5. The role of cytokines in Mycobacterium tuberculosis infection
6. The role of cytokines in congenital HCMV infections
7. The connection of cytokines and apoptosis in cardiac and haematologic diseases
8. The connection of cytokines and apoptosis in diseases with complex aetiology
9. Innate immune reactions is sepsis
10. The role of TGF-beta in breast carcinoma
B:
Molecular Mechanisms in the Development and Prevention of Chronic Infectious
Diseases
Research topics:
1. Molecular interaction between Chlamydia pneumoniae bacterium and human
cytomegalo-virus in vitro in cells of human aortic origin
2. Development of atherosclerosis in mice by infectious agents and the mechanisms
involved
3. Molecular mechanism and modulation of genetic (DNA) immunization
4. The role of cellular proteins in the molecular mechanisms of infectious diseases
5. Cellular immune response to natural cytomegalovirus infections in humans
6. Immune responses of humans and mice following Chlamydia pneumoniae or
cytomegalovirus infections
7. Possibilities of the protection of chlamydial infection
8. Adaptation of mycobacteria to the intracellular life
C: Pathogenicity of Microorganisms
Research topics:
1. Viral and host factors in the pathogenesis of prenatal cytomegalovirus infection
2. Oncomodulation by cytomegalovirus
3. Characterization of immune-response to human herpesvirus 6
4. The role of apoptosis in the patomechanism of viral infections
5. Investigation of human pathogenic yeasts and moulds on genetic level for the
development of rapid diagnostic methods
6. Molecular diagnostic of hepatitis viruses
7. Epidemiological characteristics of Chlamydia trachomatis infections in different
Hungarian populations
8. Human papilloma virus infections and their correlation with the cytopahtological
signs of the cervix
D: Antimicrobial Chemotherapy and Prophylaxis
Research topics:
1. Resistance, signal transmission in bacterial population
2. Elimination of plasmids coding for metabolic, antibiotic resistance, hemolysin or
nitrogen fixation
3. Reverse of multidrug resistance in bacteria and tumour cells
4. Occurrence and chemotherapy of multiplex tumors
5. Interactions between paclitacel and disilaxan resistance modifiers
6. Disilaxanes as resistance modifiers: in vitro and in vivo effects
7. Multidrug resistance and clinical resistance studies in testicular-, breast-, head and
neck- and ovary-cancer
8. Antiplasmid and antimicrobial effects of different oils
9. Synergy of radiation-sensitizer compounds with gamma irradiation
E: Genomics of Pathogenic Organisms
Research topics:
1. Virulence genes in pathogens of cellular origin
2. The genes of immune escape mechanisms in viruses
3. Cytokine and cytokine receptor genes carried by viruses
4. The application of recombinant viruses for vaccination
Preventive Medicine
A: Impact of Social, Economic and Life Style Factors on the Health Status of the
Population
Research topics:
1. Health status of the national and ethnic minorities in a region of Hungary
2. Impact of the school environment on the health of youth
3. The effect of screening of chronic diseases on morbidity and mortality trends
B: Experimental Investigation of Nervous System Damages Caused by Xenobiotics
Emitted to the Environment by Human Activity
Research topics:
1. Investigation of the functional and behavioural neurotoxic effects of heavy metals
and pesticide agents
2. Investigation in animal models of functional/behavioural alterations of certain
human diseases (e.g. Huntington disease) caused by neurotoxic compounds
C: Evidence Based Medicine
Research topics:
1. Evidence based medicine in the general practice
2. Evidence based medicine in the diagnostic laboratory
3. Evidence based medicine in the clinical practice
D: The effect of Physical Activity on the Physiological Conditions
Research topics:
1. Analysis of the effect of physical activity on the physiological condition in different
groups of age
2. The effect of physical activity on the gene expression in metabolic syndrome
3. The effect of physical activity on the therapeutical effects of different drugs