Team:IISER-Tirupati India/Human Practices

(Integrated) Human Practices

No research project is ever complete without feedback and inputs from experts for various aspects of the project, right from the inception of the idea and upto its successful implementation. Hence, we too interacted with a few experts from various fields of professional practice to seek their valuable suggestions with regards to our project Coli Kaze.

The iHPs followed a general flow of first a brief presentation of our project idea, followed by a casual yet insightful interview, discussion and feedback session.

We are extremely thankful that we got the opportunity to talk to such kind and grounded people, whose dedication and passion towards bringing about a difference in the world, via their respective professions, shines through.

Well, what more can we say about the experts that we were lucky to interact with? Only that they exemplify that:

‘Science makes one humble and, indeed, the humble make science!’

We welcome you to take a look at the excerpts from each of these iHPs as documented below:

Dr Viswanadham Duppatla

AVP at IKP Knowledge Park
Ph.D. Research Scholar (Biochemistry),
Indian Institute of Science, Bangalore

Project Presentation By Omkar Mohapatra

Interview By Omkar Mohapatra

Key Takeaways Possible measures for AMR awareness and valuable inputs for the implementation aspect of the project

We developed a wonderful understanding of the implementation related aspects of research through this interaction with Dr. Viswanadham.
He started by proudly remarking that IKP Knowledge Park, Hyderabad has been chosen as the Indian partner for the AMR grant-Australia, which is aimed at developing a single, scalable solution against AMR for both India and Australia.

Based on his experience, Dr. Viswanadham asserted that when it comes to combating poultry based AMR, the major roadblocks lie at the level of implementation of new policies and scientific methodologies. He, accordingly, suggested two wonderful ways to aid the implementation process. The first suggestion was to directly approach the poultry farmers, strike a friendly conversation with them about their use of antibiotics, test their farm meat and waste for the levels of antibiotic present and, if found above permissible limits, instead of punishing or imposing a fine on them, convince them to attend awareness programs on the threats of unregulated use of antibiotics and the availability of alternate, safe poultry farming methods. The second suggestion was to organise and participate in poultry, pharma and general science exhibitions, where poultry farmers could be encouraged to discuss their current farming practices and concerns, be educated about the harmful effects of prolonged and unregulated use of cheap, not easily degradable antibiotics and be pitched with alternative and safe practices and technologies, with the promise to provide them help and support during implementation. However, Dr. Viswanadham asserted that while pitching any new techniques, we must remain sensitive to the implementation cost related concerns of the farmers.

He also believes that involving the stakeholders, along with the agencies associated with the concerned area of work, right from day one of a research project would help earn the required support and trust for its effective implementation. He added that, by doing so, the poultry industry would be open to benefitting from the implementation of the proposed ideas at present rather than suffering due to stricter rules and regulations in the future.

Emphasising that failure in the proper implementation of genetic engineering and synthetic biology based solutions signifies a waste of both the skilled manpower and the huge infrastructure developed over the years in the field of biotechnology, Dr. Viswandham asserted the need to support the development and implementation of such highly potential, scientifically derived methodologies.

For our project, he advised us to use modelling and simulations to look into the individual and combined environmental effects of simultaneous degradation of multiple antibiotics and their resultant byproducts. While highly appreciating the inclusion of several genetic biosafety measures along with the use of a secure system of tanks in our project, Dr. Viswanadham signed off by asserting that our project would be immensely helpful for countries like India with high dependence on poultry farming, and applauding our team for its intent, dedication and efforts towards combating AMR for global welfare.

IKP Knowledge Park as an AMR Grant Partner:

Dr. Viswanadham started with proudly remarking that IKP Knowledge Park, Hyderabad has been selected as the Indian partner for the AMR Grant - Australia, wherein two partners, one chosen by the Government of Victoria and another by the Government of India, would be provided financial and other assistance to work hand in hand and come up with a single, scalable solution against Antimicrobial Resistance (AMR), that would be applicable and implemented across both India and Australia, by means of a potential startup.

Awareness Initiatives Surrounding AMR in the Poultry Sector:

When it comes to tackling the threat of poultry based AMR, the main problem lies at the level of implementation of new policies, strategies and technologies, remarked Dr. Viswanadham. He went on to say that, given the vastness of the Indian poultry industry, it isn’t wise to expect things to change by force, we must instead work for betterment at the level of policy making and implementation. In line with the same, Dr. Viswanadham suggested two wonderful ways of bringing about a change to combat AMR: Firstly, he suggested directly approaching the stakeholders, the poultry farmers, and striking a friendly conversation with them regarding their use of antibiotics, following with a proposition to test their farm meat/waste for the amount of antibiotics present. If found to be above the permissible amount, instead of punishing or putting a fine on the farmers, they could be asked to attend awareness sessions regarding the threats associated with AMR wherein newer, better and safer poultry farming practices and techniques could be put forth. However, while pitching any alternative measures, Dr. Viswanadham stated that, it must always be ensured that their cost of implementation is in favor of the farmers. Even if the farmers are educated on the benefits of using easily degradable antibiotics, they wouldn’t be willing to buy them because of their high costs, and the same would be the case for implementation of any other tools and techniques. Hence, a sensitive understanding of cost as the priority for farmers would go a long way in earning their trust and support. Secondly, Dr. Viswanadham advised to organise, support and participate in poultry, pharma and general science exhibitions with dedicated sections to encourage poultry farmers to reach out and discuss their practices and concerns. They could be educated about the harmful effects of the prolonged and unregulated use of cheap, not easily degradable antibiotics and could then be pitched with alternative and safer practices and measures, not just with the intent to change policies but also with the promise to help the farmers at every step while implementing them.

Now those are awesome ideas, indeed!

Scaling Up and Ensuring Proper Implementation of Projects:

Dr. Viswanadham believes that to be able to scale up and implement a project effectively, one must engage with the stakeholders and committees or agencies associated with the concerned field of work right from the beginning of the project. Taking the example of our project, he explained that poultry farming associations must be roped in for support, suggestions and getting better insight about poultry farming, which would prove to be extremely beneficial at the time of implementation of the project. As for the stakeholders in our case, Dr. Viswanadham remarked that involving the poultry farmers in the entire process, starting from the conception of the idea upto its implementation, from day one, would help them to develop an understanding of the problem, realise the necessity for change, grasp the working and advantages of the proposed alternative, and consequently build trust for the implementation of the idea. He added that the poultry industry would be very open to suggestions on learning about the disadvantages of current practices and the benefits of the alternatives as the farmers would prefer to have a slight increase in the cost of their product and implement the proposed ideas at present, instead of having to face severe problems in the long run, in case stricter regulations are put in place in the future.

Implementation of Synthetic Biology Based Solutions for Global Welfare:

Stating that dedicated investments towards development of knowledge, infrastructure and training opportunities in the field of biotechnology, over the years, have resulted in the availability of advanced technologies as well as dedicated, responsible and skilled manpower, Dr. Viswanadham remarked that there is immense potential for Genetically Modified Organisms (GMOs) and other synthetic biology based solutions in tackling real world problems. Pointing out that failure in the proper implementation of such approaches signifies a waste of both the skilled manpower and huge infrastructure, he asserted that GMOs as well as synthetic biology oriented research and its ultimate implementation must be highly supported and encouraged.

Project Coli Kaze:

Appreciating our project for including multiple biosafety measures at the level of genetic engineering along with the use of a secure system of tanks, a standard part of most effluent treatment plants, Dr. Viswanadham advised us to use modelling and simulations to also look into the various possible byproducts, and their individual as well as combined effects in the environment, following the degradation process of one or more antibiotics.
Dr. Viswandham concluded by praising us for our intent, dedication and efforts towards combating AMR for global welfare and asserted that our project would prove to be immensely beneficial, especially for countries like India with a huge poultry farming industry.

Dr Sangram Bagh

Project Presentation By Tejas Vandeo Borkar

Interview By Uddeshya Pandey

Key Takeaways Possible measures for AMR awareness and valuable inputs for the implementation aspect of the project

We spoke to Dr. Sangram Bagh from Saha institute of Nuclear physics to get his views and suggestions on our project design. Dr. Bagh works primarily in the synthetic biology field therefore we reached out to him for expert opinion. We began by giving him a short presentation of our project modules, post which we had a detailed discussion session on various aspects of our project.

The first point he suggested was that it is important to find out the concentration ranges of the various sulfonamides in the excreta. This will help in estimating the amount of bacteria required to degrade a particular quantity of sulfonamides and also helps in designing the tank for the final setup. We integrated this input in our literature survey.

Secondly, he pointed out that the araBAD promoter system is leaky, so it can easily be expressed. It is therefore essential to optimise the ribosome binding site (RBS). To achieve this he suggested us to design a set of ribosome binding sites (library) and then choose one amongst them that best suits our model.

He also highlighted that since the slurry will have multiple antibiotics, it is crucial to specifically stress that this proof-of-concept system can be extended to other antibiotics too, this will help in clearing any biosafety concerns of the project that one might have.

Lastly, he advised that we look into the logistics and cost calculations of the tank so that we can build a tank will be able to sustain in the market along with other cheaper chemicals. He also suggested we include as many parameters as possible like the length of the tank, diameter etc. while designing the tank for the slurry treatment.

How did this help coli-Kaze?
Discussion with Dr. Sangram helped us validate the modules and the gene circuits we designed for our project. His suggestions helped us contemplate about a few aspects that needed further improvements. In his conclusion remarks, Dr. Bagh appreciated our project idea and also expressed that he liked the way different things were incorporated while designing the entire project.

Dr Abdul Ghafur

Coordinator of the Chennai Declaration on Antibiotic Resistance, MD MRCP FRCPath, Consultant in infectious diseases at Apollo Hospital, Chennai

Project Presentation By Amogh Desai

Interview By Purva Naik

Key Takeaways Antibiotic Resistance: the causes, the stats, and the possible solutions

This wonderful interaction session with Dr. Ghafur was dedicated to understanding the complexities of the Antibiotic Resistance (hereafter, AR) saga. As opposed to the popular belief that the extent of antibiotic consumption solely directs the development of antibiotic resistance, Dr. Ghafur asserted that the type of antibiotic, the duration and dosage of its consumption, and the type of bacteria, all play a key role. He emphasised that factors like large population, socio-economic disparities, severe sanitation related issues, etc. make India’s antibiotic usage related challenges very different from those of the western countries. Dr. Ghafur explained how many Indian medical societies, realising the consequent need for India’s own antibiotic policy, came together to draft a joint recommendation in 2012 on how to tackle AMR in India in the form of the Chennai Declaration, with the primary aim of supporting the then government to effectively reimplement the National Antibiotic Policy of 2011.

He then put forth a global statistical picture of AR, asserting that about 70% of the antibiotic usage is in animal husbandry. Of the remaining 30%, over-the-counter use accounts for about 15%. Even if half of the remaining consumption is based on irrational prescriptions, it equals to just 7.5%, which is relatively a very small percentage of the total antibiotic resistance burden. Hence, Dr. Ghafur emphasised the need to prioritise educating the public, and not just the doctors, about the dangers of irrational use of antibiotics along with the need for proper sanitation measures, the lack of which worsens the AR crisis.

Dr. Ghafur believes that antimicrobial resistance (AMR) is a very complex challenge and requires complex solutions. In addition to counselling patients to finish their prescribed antibiotic courses, over the years, doctors have reduced the duration of these courses. While it may take several years or decades to ban antibiotic overuse and even growth promotional use in animal husbandry, there is an urgent need for people/teams like us to bring about alternative scientific solutions to combat AR, and AMR in general, asserted Dr. Ghafur.

He stated that we have essentially run out of antibiotics to treat severe bacterial infections and until new antibiotics are developed against multidrug resistant and pan resistant bacteria, combination therapy is the only way out, though it also increases the cost of treatment. Dr. Ghafur added that while COVID-19 is killing people worldwide, it is also an excellent opportunity for activists and experts to discuss about AR, a silent killer behind the ongoing pandemic, (due to the extensive use of antibiotics to treat COVID-19 related secondary bacterial infections), and even AMR, because people now respect microbes and understand the importance of infection control through simple hygienic measures like washing hands properly. In this sense, Dr. Ghafur regards COVID-19, and other viral outbreaks, an indirect blessing, and very rightfully so!

While there would always be some concerns with regards to synthetic biology and genetics, in general, Dr. Ghafur believes that we, as practitioners of science, can ensure its development only by continuing to delve into its depths, albeit responsibly and while taking all necessary precautions.

Dr. Ghafur concluded by emphasising that our project idea is very good and, if successfully implemented in countries like India with a huge poultry farming industry, it could prove to be extremely useful in reducing the multidrug resistant bacterial contamination of the environment. He remarked that what youngsters like us are doing, by developing such scientific methodologies and practical solutions, could go a long way in combating AMR globally.

The Root Cause of Antibiotic Resistance:

Dr. Ghafur started by first clarifying a common misconception that the probability of occurrence of antibiotic resistance (hereafter, AR) is governed simply by the extent to which a certain antibiotic is consumed; the type of antibiotic, the duration as well as the dosage of its consumption and, most importantly, the bacteria in question - all equally influence the probability of development of AR in humans (animals, in general). He added that previously doctors used to counsel their patients that if an antibiotic is prescribed to them, they must finish the course because if they don’t, the bacteria would become resistant and the drug may not be effective in the future. While the counselling is still very much prevalent and pertinent, over the years, the duration of the prescribed course has come down significantly. The lower the dosage, but the higher the consumption of the antibiotic, the more the chance for a bacteria to become resistant. Hence, it’s not the overuse but the misuse of antibiotics that leads to resistance, asserted Dr. Ghafur.

The Chennai Declaration:

Dr. Ghafur has been an integral part of the formulation of the Chennai Declaration and he briefed us about how it actually came into being. He remarked that, in India, the National Antibiotic Policy was put out in 2011 but there was no serious effort for its implementation in the country then. So, many medical societies of india, like the infectious diseases society, the surgical society, more than half a dozen other medical societies, along with NABH, ICMR, Drug Controller General of India and many other stakeholders, came together to draft a joint recommendation on how to tackle AMR in India in the form of the Chennai Declaration which was published in 2012 and submitted to the then government of India. This helped restart discussions at the highest level with multiple meetings held on how the recommendations could be implemented with the Union Health Ministry.
Dr. Ghafur justified the need for India’s own antibiotic policy by stating that India is a country with 1.3 billion people, many states, socio-economic disparity and the huge issue of sanitation. Indian challenge is very different from those of the western countries and thus, India cannot follow their policies. The aim of the Chennai Declaration, hence was to convince the then national union government that India too could implement an antibiotic policy and that all the stakeholders understood the limitations of and were willing to support the Indian government. This inspired the reinitiation of the implementation of the National Antibiotic Policy of 2011.
Accordingly, two Chennai Declaration documents were prepared - one original document and then as the government started implementing the antibiotic policy again, realising the need for time bound targets, another document as a five year plan was prepared to implement the National Action Plan (NAP) for AMR [released in April 2017] - the National Antibiotic Policy.

Urgent Need for Measures to Combat AR:

Dr. Ghafur stated that the medical and scientific communities’ belief that doctors are probably responsible for 80% of the AR globally and that AR can be tackled if the doctors prescribed medicines sensibly and rationally has changed over the last 10 years with increased awareness about the causes of the problem. He, accordingly, led us into some stats surrounding AR across the globe. About 70% of the global antibiotic use is for growth promotional purposes in animal husbandry. This leaves 30% for human use, out of which half of it is accounted for over-the-counter use without doctor’s prescription. Of the remaining 15% attributed to prescription by doctors globally, if even half of it is considered irrational, that amounts to only 7.5%, which is comparatively a very small percentage of the total. Hence, to tackle AR, instead of just educating and recommending doctors to prescribe antibiotics rationally, we actually need to educate the public - farmers, the government, politicians, media, patients, school children - about the dangers of irrational use of antibiotics and the necessity to reduce their over-the-counter use because it is the public and not the doctors who is the most important stakeholder of the AMR saga, asserted Dr. Ghafur. He added that besides developing a culture of rational antibiotic usage, there is an urgent need for measures to improve environmental sanitation, especially in developing countries like India where lack of sanitation is one of the most important determinants of AMR, because unless there is an improvement in environmental sanitation, whatever is done on rationalising antibiotic usage will be largely ineffective.
Dr. Ghafur believes that AMR is a very complex challenge and requires equally complex solutions on various fronts. He remarked that while the primary solution for the problem would be to ban the overuse of antibiotics (like the ban on the use of colistin as a growth promotional agent by the government of India), it cannot be done for all antibiotics and it would take several years or even decades to completely ban at least their use as growth promotional agents. Meanwhile, he asserted, there is a need for people/teams like us, who would bring about practical solutions and develop scientific methodologies to reduce the environmental contamination with antibiotics, and what youngsters like us are doing is just one but a very important component of the AMR saga.

Oh, how motivating is that!

Combination Antibiotic Therapy:

Dr. Ghafur remarked that where earlier only one antibiotic could be used to treat an infection, nowadays, a combination of two or even three antibiotics is required, though not for all infections, mostly for severe infections. He added that in his own long clinical practice, there have been times when, in case of severe infections, one or two antibiotics have worked while, at times, not even a single antibiotic has been effective and hence he believes that we have reached a stage where we essentially don’t have antibiotics to treat bacterial infections. Although it’s still controversial whether combination therapy is really the way forward, there is enough evidence to suggest that, in case of severe infections with multidrug and pan resistant bacteria, combination therapy helps. Dr. Ghafur insisted that it’s really a paradox because, though it increases the cost of therapy, until effective antibiotics are developed against resistant bacteria, combination therapy is the only way out.

COVID-19 - An Opportunity:

AMR is a silent killer for COVID-19 patients. Many COVID-19 patients develop secondary bacterial pneumonia and other infections whereupon doctors have to prescribe a lot of antibiotics and so antibiotic usage, including overusage, is a serious problem during the ongoing COVID era, asserted Dr. Ghafur. He added that, while COVID-19 is killing patients around the world and would also lead to a tremendous increase in the spread of AR, it is also an excellent opportunity to discuss AMR because now everyone knows about the importance of infection control and respects microbes, viruses and viral outbreaks. Efforts made over the years to convince people, especially the healthcare workers, to wash their hands properly largely failed, but the ongoing pandemic has made the whole world wash its hands properly and, in that sense, COVID-19 is an indirect blessing, remarked Dr. Ghafur. He believes that such viral outbreaks are opportunities for activists and experts to convince the government, politicians and the public about the importance of tackling microbes, and that now is the right time to talk about the dangers of resistant superbugs and how AMR is as serious a problem as COVID, Nipah or Ebola.

Synthetic Biology and Genetic Engineering:

Dr. Ghafur remarked that while people like him will always be a little concerned about genetic engineering because it may create superbugs, one shouldn’t be afraid to cross the boundaries and do genetics based research. Adding that science cannot develop if we, as its practitioners, are hesitant and afraid, he stated that the only thing we should keep in mind is that we must take all necessary precautions and do responsible research so as to, as he laughingly said, ‘prevent the generation of Frankensteins’.

Project Coli Kaze:

In his concluding remarks, Dr. Ghafur emphasised that our project idea is really good and restated that what youngsters like us are doing is a very important contribution towards combating AMR. He asserted that if we are able to successfully implement our project in poultry farms, especially in countries like India where there’s a huge unregulated use of antibiotics, it could play a major role in reducing the multidrug resistant bacterial contamination of the environment.

Dr V Bala Subramanian

Co-founder and Director at Bugworks

Project Presentation By Shubhrika Jain

Interview By Amogh Desai

Key Takeaways Setbacks in the development of new antibiotics, importance of dry lab and essential suggestions for the project design

Dr. Bala (as he is fondly addressed) gave us an extremely useful insight into the development of antibiotics and the various crucial aspects of biological research. He started with reasoning that, although many potential targets and their respective inhibitors have been identified, the challenge of getting the inhibitors to pass the bacterial envelope as well as the wide variety of efflux pumps kicking them out have proved to be major roadblocks in the development of new antibiotics against gram negative bacteria.

His team at Bugworks has successfully overcome these two roadblocks and has developed a brand new class of stand alone, highly potent antibiotics against gram negative bacteria, which works even better against the gram positive bacteria, i.e, a true broad spectrum, the first of its class since the fluoroquinolones. They have basically generated a chemical entity with reduced binding affinity for the binding pocket of the AcrB subunit of the AcrAB-TolC efflux pump system but with high potency against the targets gyrase and topoisomerase IV.

Dr. Bala went on to emphasise the importance of computational biology, modelling and simulation as core components of modern day biological research. He justified that they prove to be of utmost use at various levels during research - for understanding biological pathways and the underlying genetic principles, for identifying potential targets and respective anti-entities, for determining chemical vulnerability and studying drug pharmacokinetics and metabolism, for analysing molecules of interest at the level of functional domains and, most importantly, for determining off-target effects and making safety predictions.

Dr. Bala believes that while we, as researchers, must be wary of the strong concerns surrounding synthetic biology and genetically modified organisms (GMOs), it should not prevent us from carrying out responsible research into these areas which have tremendous potential in the fields of nutrition, healthcare, environmental clean up and many more.

With regards to our project, Dr. Bala suggested that we look into the environmental effects of the various possible byproducts of antibiotic degradation and also pay attention to the scaling up factors of the project, as the thermodynamic and enzyme kinetic principles exhibit drastic changes on shifting from a microtiter plate to a barrel.

Dr. Bala appreciated the project design, especially for being centered around a close and safe system of slurry tanks, and also for including a modular drug degradation cassette which could be easily switched to target any other antibiotic, or even drug, in general. He also emphasised on our project being very timely with regards to the severe antibiotic resistance threat lurking behind the ongoing COVID-19 pandemic. Hence, all of this promised wonderful applications of our project in combating AMR for the sake of healthcare and global welfare.

Challenges in Developing Antibiotics against Gram Negative Bacteria:

According to Dr. Bala (as he is fondly addressed), one of the biggest challenges in developing antibiotics against gram negative bacteria has been that of actually getting them into the bacteria and he asserted that it is definitely not because of the lack of efforts by researchers. He reasoned that, despite the identification of several essential targets and their respective inhibitors, making the potential inhibitors pass through the envelope as well as the wide variety of efflux pumps of gram negative bacteria kicking them out have proved to be major roadblocks in the development of new antibiotics against the gram negative bacteria.

Bugwork’s New Class of Antibiotics :

In response to our curiosity about his work at Bugworks, Dr. Bala enthusiastically took us through Bugwork’s journey-so-far of developing a new class of antibiotics against gram negative bacteria. His team started with focussing on the major family of efflux pumps, the RND family. They worked around its prototype in E. coli called the AcrAB-TolC efflux pump system, where AcrB has the binding pocket for the chemical entity being tested and TolC acts as the “sewer pipe” that actually kicks the entity out, while AcrA anchors them both. They picked those entities within the bacteria as the chemical starting points that were impacted only by AcrB knockout and then they went about reversing the chemistry to have an entity with reduced binding affinity to AcrB but high potency for the well established targets, lo and behold, gyrase and topoisomerase IV. With this delicate balance between losing the binding affinity on one hand and retaining it on the other, to deal with the lipophilicity, the team worked with logD values of about one.
And what now is the outcome of all of this? Bugworks has developed a brand new class of stand alone, highly potent antibiotics against gram negative bacteria, which works even better against the gram positive bacteria, i.e, a true broad spectrum, the first of its class since the fluoroquinolones.
While excitedly informing us that they are just about to enter clinical development and hope to have their first compound’s phase I studies in the following 2-3 months, Dr. Bala remarked that as the compound is super potent on gram positive bacteria, works on other mycobacterial strains like avium as well as other non-tuberculosis strains and has shown no exceptions at all, he is confident that it would be effective even against M. tuberculosis.

Now, how awesome is that!

Importance of Computational Biology, Modelling and Simulation:

Dr. Bala emphasised that not just modelling and simulation but also, and majorly, computational biology are core to biological research. They prove to be of utmost use at various stages during research - for understanding of biochemical pathways to identify pressure points in terms of targets through bacterial physiology based modelling, for studying drug pharmacokinetics and metabolism by analysing population behaviour in response to being challenged by a chemical entity, for determining chemical vulnerability, i.e., identifying most effective targets with lethal biological effects using reaction kinetics, for functional domain level based analysis in polypharmacology to identify structural similarities among potential targets so that they could be targeted with a single chemical entity, and finally, and most importantly, for safety predictions to determine the off targets and evaluate their binding characteristics to the chemical being tested.

Controversy Around the Use of Synthetic Biology to Tackle Real World Problems:

Not all of the concern surrounding the use of synthetic biology, and in fact, Genetically Modified Organisms (GMOs) in general, is rational, believes Dr. Bala. He went on to remark that he feels that synthetic biology has tremendous potential with powerful applications in the field of nutrition, healthcare, environmental clean up and many more. While we, as researchers, must always be wary of the fact that there is a clear large lobby with very strong opinions against such manipulations, it should not prevent us from venturing into those areas and carrying out responsible research because opinions do change over time, added Dr. Bala.

Project Coli Kaze

When Dr. Bala suggested that we include biosafety measures with respect to transduction, we reassured him that we were working on it and it remained one of our primary focuses. He asked us to look into the environmental clearance requirements set out by the government, for the implementation of the project, as well as the various possible byproducts which would be formed following antibiotic degradation, along with the effects they have in the environment. While stating that, on shifting the experiments from a microtiter plate to a beaker and then to a barrel, the thermodynamics and enzyme kinetics, that appeared to work beautifully in a microtiter plate, change drastically and do not seem to work any more, Dr. Bala advised us to be careful with the scaling up aspects of our project.
Appreciating the project design for having been centered around a closed, safe system of tanks as well as for having a modular cassette that can be easily switched to target any other class of antibiotics, he stated that our project could have very nice applications. Dr. Bala also remarked that, based on the current data from hospitals that Bugworks has associations with, about 50% of deaths amidst the ongoing pandemic are actually estimated to be caused by secondary bacterial infections, and thus, he believes that our project is very timely and could prove to be immensely useful in the field of healthcare by combating AMR. Stating that our project was amongst the few good projects that he has come across, Dr. Bala signed off by saying that he hopes that our team members would put their heads together to establish a startup down the years.

And now, how encouraging is that!

Dr Raghunath O Ramabhadran

Assistant Professor, Department of Chemistry at IISER Tirupati

Project Presentation By Ved Mahajan and Amogh Desai

We decided to take help from one of our faculties from our institute to critique our model and suggest necessary additions that we can make to our model so that it best replicates the real scenario.
After we explained our projects main theme and what we want from the model, The following changes were suggested:

  • 1. Look for equations describing different kinetic equations as our enzymes mechanism is not known.
  • 2. Introduction of two extra parameters to include the fact that our enzyme is a bisubstrate enzyme.

Apart from this, he helped us to perform docking and molecular dynamics simulation and interpret the results. We earlier had used a monosubstrate kinetics equation. As per his instruction, we looked into bi-substrate enzyme kinetics equations. We found two mechanisms that are likely to be followed: ordered bi-bi and random bi-bi. Of the two parameters he suggested, one was to cover up for one unknown kinetic parameter for the other substrate and another one for reducing the efficiency of the maximum rate of our enzyme as our enzyme would be working in a natural environment.