After spending his entire research career at the National Institute of Immunology, New Delhi, Dr M Ayub Qadri has joined IUST as Dean of Sciences. In a free-wheeling conversation, he details his long journey to understand the pathogens that trigger typhoid
KASHMIR LIFE (KL): What challenges have been there to immunology after Covid19?
DR AYUB QADRI (DAQ): The challenges have remained unchanged. Immunologists continue figuring out how pathogens – viruses, bacteria, and parasites, interact with the human body.
The immune system of any organism is like a defence system. It tries to clear out the infections in our body but sometimes these pathogens through trickery and falsity weaken and overcome the immune system. It changes the entire defence system and actually uses the human body for the growth and proliferation of the infection. That is how the viruses have been doing throughout.
KL: Before we get into your core competence, can we know about your learning curve?
DAQ: It was smooth and beautiful because of my teachers and mentors. From my schooling to my university days, my educators made everything interesting and absorbing for me and that helped me develop an interest in research. I qualified for high school at Sekidafar Higher Secondary and then I went to Islamia College and Kashmir University for higher education.
For a short duration, later, I was paced at the Regional Research Laboratory of Jammu. Eventually, I went to the National Institutes of Immunology, Delhi.
During my master’s at the University of Kashmir, I deepened my interest in biomedical sciences. I also learned that biomedical research ultimately boils down to chemistry. If one understands the chemistry of molecules, it will be easier for him to understand the chemistry of pathogens, cancers, and other maladies.
My journey of research has been very exciting and from the field of chemistry to biology to biomedical sciences and immunology everything has been very compelling to me.
Until my Master’s, I never went out of Kashmir and after that, I decided to get out for some exposure. I went to different institutions like TATA Institute of Fundamental Research, Bombay, Centre for Cellular and Molecular Biology, Hyderabad, and then All India Institute of Medical Sciences.
My parents have played a major role in my education. For most of the twelfth graders, there were two initial options – a doctor or an engineer. I had two more – veterinary and agriculture. For some strange reason, I was not able to opt for veterinary, so I got into agriculture. However, I found no interest in it and my parents also realised that. They advised me to do what I was fond of.
Then I moved to the National Institute of Immunology, AIIMS, where I started my PhD. My mentors provided an environment of opportunities to me. At that time, top immunologists were invited to interact with us for exposure and experiences and to get to know more about things. We had the best teaching for immunology at that time.
KL: What were the major takeaways from your PhD.?
DAQ: When I was in Jammu, for some research project, I read an article about immunology that elucidated the discovery of antibodies. It endorsed the monoclonal antibodies and how they can be efficient for treatment and diagnostics. So, that enhanced my keenness regarding the research on antibodies, and then eventually I went to the National Institutes of Immunology for the doctoral programme and started my experimentation.
My idea was to make monoclonal antibodies for (Salmonella typhi Bacteria) a pathogen, known to cause typhoid. At around that time in 1984, George Kohler and Cesar Milstein invented a technology for the production of monoclonal antibodies through, what is called, the hybridoma technology that transformed and modified the science field, diagnostics, biomedical research, and even therapeutic diagnosis. So, with that reference, I took my area of concern to make antibodies for typhoid pathogens.
With the technology, we can reduce the method and time of diagnosis from 72 hours to less than 24 hours. These measures then allow doctors to improve the prognosis and medication process. So, I was able to generate some very good antibodies for the pathogens which proved to be quite appropriate for diagnostic purposes.
The second takeaway was, understanding how these pathogens interacted with the cells inside the body and how they responded to the antibodies.
KL: Was your research and the reagents that you developed applied in the market?
DAQ: Yes, they were determined. During my PhD, the interaction with pathogens was considered unidirectional. For instance, if a person gets an infection, his/her body reacts to that. Similarly, like a human, the live pathogens inside the body do respond. We try to clear them out but they modify and change themselves. During the research, we saw that, if this pathogen is mixed in water, it has a different reaction and while having it in a food matter, it responds differently. It has an alteration in behaviour concerning blood, spleen, or other components.
The reagents that we have generated have been very useful in understanding this phenomenon.
Whenever we get an infection, our immune system senses danger. The pathogen becomes quite acute at first and our body reacts to that. As the infection progresses, the pathogen decreases its intensity, so that we do not get the actual potency of danger. It establishes itself inside without signifying symptoms and slowly converts into a disease.
KL: What were your further accomplishments before coming to IUST?
DAQ: After my PhD, I decided against going for a post-doc promptly and fortunately after I submitted my PhD thesis, I got a job offer from the National Institute of Immunology, India.
Later, I went for my post-doctoral research at the South-eastern Medical Centre at the University of Texas, USA.
The question was what can I do as an independent investigator or a researcher? So, I decided to take the same typhoid pathogen and work on infection and immunology.
The study that I did was that when the pathogen is consumed through food or water, it goes straight to the intestine. There, it marks a hole in the cells and gets in. When it grabs the cells, it subsequently affects the blood and captures other organs like the liver, gall bladder, and spleen as well.
I worked on how the pathogen interacts with the epithelial cells of the intestine and the immune cells of the body. As the immune system is well known for clearing out toxic and infectious microbes, our study focused on what affects the immune system to not function properly and not work against pathogens. We also emphasized on what can be the possibility of a pathogen overcoming the immune system.
Apart from that, the typhoid bacterium only affects the human body and no other living creature, and there is no experimental model to study the disease. In that case, we also wanted to understand what the reasons are and why it does not affect the other life forms. Furthermore, we also evaluated whether we get immunity after overcoming the pathogen or not.
During my entire career and at the NII, I spent years understanding immunology, using the typhoid pathogen as a model system.
As I mentioned earlier, our immune system senses all infections as a danger. In molecular terms, that danger has a reference. For example, in the typhoid pathogen, Salmonella typhi, there is a molecule present. And whenever we get an infection, our immune system specifically senses the same molecule. As soon as it senses, our system starts reacting to it and produces altering inflammatory responses or innate immune responses.
As the infection progresses, the pathogen closes and wraps up the molecule. And because of that our immune system is not able to further perceive it, which then allows the pathogen to establish infection. We have tried to understand this strategy through molecular terms and we are continuing and trying to understand this particular approach.
Another aspect that we understood was that the immune system has different parts, like the innate immune system and the adaptive immune system. With antibodies, there are more cells like T cells, which are an important component of the immune system and have a crucial involvement. In our experimental model, we figured out the mechanism and how pathogens make the T cells, in a way dysfunctional which leads to the failure of the system.
The main thing that we have achieved from all the experimentations is that we are now able to understand and we now know what type of vaccine should be made against this type of pathogen and what should be its characteristics. Though we have vaccines available for it, by going into detail, we can also make an efficient and better vaccine through the study.
Besides, similar strategies might be existing in other bacterial pathogens as well. We are trying to figure out these types of studies here in IUST in tuberculosis pathogens.
… Umaima Reshi processed the interview