Kuntal Pal, Author at Adamas University

#GenomicsPlus #BiotechnologyPlus Genomics- a tool to combat the second wave of Coronavirus pandemic

While the world is facing a new type of biological war after world war-II with corona pandemic caused by coronavirus a piece of positive news struck me two weeks back. New Zealand declares that their country is corona free. With more days in lockdown and staying back at home, communities are fighting on psychological platforms while countries are fighting with their sharp decline in economies. In between all that many countries like South Korea, Taiwan, and New Zealand were able to successfully suppress the first phase of infections and trying to prevent the second phase of COVID-19 pandemic with a very old tool of Biological sciences called “Genomics”.

Scientists around the world are poised to identify the origin of the second wave of infection using Genomics with very advanced tools commonly available in our research institutes. Genome sequencing of first coronavirus strain isolated from Wuhan, China was published on 11^th Jan, 2020¹. Currently, 35000 viral genome sequence of human SARS-CoV2 is available online with a constant increase in their number². These massive data of viral genome sequencing from different countries:

1) Allows the scientist to understand the origin of the viral outbreak in their own country.

2) Able to identify the genomic variability among different strains may be responsible for a higher or lower rate of pathogenicity.

3) It further helps to contain the spread of the virus by identifying the contact tracing and its geographical origin³.

4) Identifying a specific strain by genomics guide the medical practitioners for precision intervention targeting that particular strain to reduce the spread of infection at a very early stage.

Recently, an analysis published in the journal “Cell” shows a particular mutated variant of the virus is more transmissible compared to other genetic variant⁴. The genetic variant carrying a mutation in the spike protein region was accounted for just 10% infection in March identified from the sequencing of patients. Dynamic tracking of this coronavirus variant by eminent Joint Consortium of Genomics from Los Alamos National Laboratory the USA and the University of Sheffield, UK identified its global dominance by May accounting for 78% cases around the world. Probably, the mutation in spike protein improves the virus uptake by human cells.

Generally, RNA viruses are prone to mutation and every year we need a new version of the vaccine for flu. Although, the authors in Cell paper did not identify the reason for the high transmissibility of this coronavirus variant among humans the genomic study was successful to identify highly infectious variants. Similarly, identification of mutants which can make virus unrecognizable by our immune system or making it more stable so that it can survive in the air for a longer period will be able to reduce the chances of community spread.

Figure: Nextstrain software platform performs easier and faster representation genomic epidemiology data. The above figure is adopted from Bedford Lab webpage showing the genetic epidemiology of140 novel coronavirus strain (genomic data available at www.gisaid.org) in early March.

During the last decade, genome sequencing techniques have evolved largely due to rapid improvement in technology and operating software. Thanks to Human Genome Project mainly carried out by NIH, the USA in association with other renowned labs around the world completed in 2001-2002 contributed to the rapid development technologies in Genomics. Next-generation sequencing technologies and instruments like Illumina’s Solexa Sequencing or Roche 454 sequencing offered by several companies markedly reduces the time requirements of genome sequencing as well as costs. It is several folds cheaper to do a genome sequencing today in comparison to twenty years back which further opens the gateway for personalized medicine by genome sequencing. Therefore, the requirement for trained peoples in the field of Genomics is rising to operate the instruments, data analysis, and statistical calculations required for a conclusive study.

References:

1.Zhang, Y.-Z. & Holmes, E. C. A Genomic Perspective on the Origin and Emergence of SARS-CoV-2. Cell 2020; 181, 223–227.

2.https://www.gisaid.org/.

3.Stevens, E. et al..The Public Health Impact of a Publically Available, Environmental Database of Microbial Genomes. Front. Microbiol. 2017;8, 808.

4.Korber, B., et al..Tracking changes in SARS-CoV-2 Spike: evidence that D614G increases infectivity of the COVID-19 virus. Cell 2020; https://doi.org/10.1016/j.cell.2020.06.043.

Biotechnology or Microbiology? What to Choose?

Biotechnology and Microbiology are two major disciplines of Biological Sciences with a diversified application related to their domain. Biotechnology refers to a field dealt with the manipulation of living organisms at the molecular level through recombinant DNA technology also known as genetic engineering to form useful products for the betterment of mankind. Microbiology is an area of science exploring the world of microbes in terms of their genomics and proteomics and their applications in food, pharmaceutical, and biotech industries. In the historical perspective of biological sciences Biotechnology and Microbiology developed in parallel. The age-old method of fermentation technology in which microorganisms were used to produce commercially important products is an example of collaboration between these two fields. Understanding the science behind naturally occurring fermentation of sugar and fruit mashes to alcohol by microbes comes under Microbiology. Biotechnology later took the credit of developing the fermentation technology for mass production and commercialization of alcohol. This article is going to provide an outlook on these two important courses in terms of knowledge, application, and job prospects.

The course of Biotechnology drives with a vision of “Heal the world”, “Fuel the world”, and “Feed the world.” Several discoveries and developments 1950 onwards revolutionize the process of genetic engineering when scientists were able to modify the genome of microbes, plants, and animal cells for recombinant commercial production of biomolecules and other purposes. With the rapid growth in world population biotechnology is an important domain to `answer the challenges of food and nutritional requirements, diagnosis and treatment of diseases and fuel needs. Studying biotechnology have the advantage of covering several different disciplines like general biochemistry, genetics, microbiology, molecular biology, etc. The knowledge in those different disciplines nurtures the mind of biotechnologists for innovations. The subjects of animal biotechnology, nano-biotechnology, and microbial biotechnology are useful to learn the techniques for designing new targeted drugs for the treatment of diseases with low side-effects and devising new smart nano-sized tools for early diagnosis. Similarly, in plant biotechnology, genetically modified plants developed in labs can empower mankind for increased production of highly nutritious food with a low spoilage rate. Biotechnology also uses fermentation technology of microbes in the production of biofuels like alcohol and bio-hydrogen thus reducing the dependency of society on petroleum like conventional fuels.

Microorganisms are present everywhere around us, on us, and within us and play vitally important roles for maintenance of life on earth. Microbiology is a science to understand the biochemistry, genomics, proteomics, pathophysiology of invisible microbes for their application in food, fermentation, pharmaceutical, and biotech industries. Microbes include bacteria, fungi, viruses, prions, protozoans, algae and they have an important participation in nutrient cycling on earth, biodegradation/bioremediation, food-spoilage, disease pathogenesis, and analysis of climatic changes. Studying microbial biochemistry and genomics helps microbiologists to understand the biological mechanism of these microbial lives. On the other side Food technology, microbial biotechnology and industrial microbiology subjects focused on the application of versatile microbes in industries such as the development of vaccines, antibiotics, dairy, and food supplements (probiotics). Microbiology also helps us to understand the microbial diversity and their evolutionary aspects of life on earth. It can answer a big question on the emergence of the first life on earth. Currently, the researchers are trying to identify the function of the microbiome (microbial population in our gut) in combating cancer, Parkinson’s, and Alzheimer’s diseases.

Thus, Biotechnology and Microbiology both seem to be close and interlinked to each other, there are differences when it comes to jobs and prospects. As we have seen that biotechnology depends partly on different laboratory methods of microbiology, but the applied part of microbiology is completely dependent upon biotechnological methods. Therefore, a bachelor degree in Biotechnology can pave the way of aspirants to a various different area of work which may include industrial processes in different types of industries (agricultural, pharmaceutical and medical), research and development along with management jobs, while Microbiology degree can offer you jobs mainly in research and development and some specific industries. B. Tech degrees in Biotechnology with initial exposures to engineering subjects like computer sciences and electronics open their job prospects in bioinstrumentation and bioinformatics companies. Currently, MBA in Biotechnology (followed by B.Sc. Biotechnology) is another new and upcoming course offered by several Indian Universities. With the rapid growth in new start-ups on biotech, the job market in India is attractive with more requirements of biotech professionals in labs as well as managerial positions.

The students seeking their career mainly in research with the aim of Ph.D.degree in the future also carries the advantage of having a degree in Biotechnology. Due to the diverse nature of the Biotechnology discipline, the students can more easily switch to other closely related biological science subjects for Ph.D., which can’t be so flexible with a Microbiology degree. There are many Fellowship programs of monetary funding for scholars pursuing a Ph.D. in India, offered by DBT-JRF and CSIR-NET. Further with a master’s degree in Biotechnology and Microbiology, students can also apply for Ph.D. in highly reputed foreign Universities. Former Prime-Minister of India recognized the importance of Biotechnology for the common people of India and established the Department of Biotechnology (DBT) as a part of the Ministry of Science and Technology. DBT is responsible to fund important research going on different institutes all around India. In conclusion, it must be said that both areas offer good career prospects with a bit of an advantage on the Biotechnology side. However, it is the personal interest of a student which ultimately drives their way to the summit of a professional career.

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MICRONEEDLE BASED VACCINES DELIVERY IN THE ERA OF NANOBIOSCIENCE

Student coordinator: -Rahul Dutta, Srijani Basak (3^rd-year B.tech biotechnology)

Nano-biotechnology is one of the fascinating and latest areas of science dealing with the conceptualization and designing of biological machines at the nanoscale level. The application of these biomachines also known as nanobots may vary from targeted drug delivery to real-time diagnostics. The nanoscale size of nanobots provides them easy access to targeted areas through the blood circulatory system and its biological origin reduces side effects largely post-application. In Adamas University, Nano-biotechnology is a part of the curriculum for the students of B.Tech Biotechnology.

The novel coronavirus SARS-CoV 2 (Severe acute respiratory syndrome coronavirus 2) isolated from Wuhan, China is posing a challenge to the scientific community and mankind throughout the world. It’s a mutated version of earlier identified similar viruses like SARS-CoV in 2003 and MERS-CoV in 2014 all belong to Coronaviridaefamily. The World Health Organization (WHO) coined this disease as COVID-19 and also declared it a pandemic in March 2020. COVID 19 common symptoms are – Fever, dry cough, shortness of breath which leads to severe acute respiratory syndrome that can turn fatal in a comorbid condition of the patient.

The primary virulence factor of SARS-CoV 2 is the surface Spike(S) protein. The S-protein is susceptible to mutations which bind strongly to the angiotensin-converting enzyme (ACE2) receptor present on the cell surface of the respiratory tract epithelium. ACE2 binding mediates the entry of virus particles into the cell cytoplasm where it undergoes replication. The coat protein then synthesized is a product of the translation of the RNA. Once fully assembled the virus particles are released from the vesicles. In the lungs, the virus infects trachea, bronchi which triggers inflammation. Subsequently, it damages the alveolar lining which causes fluid leakage in the alveoli and hinders oxygen exchange, leading to a reduction in oxygen saturation.

Among the increasing number of COVID-19 related casualties worldwide, a glimpse of hope and success can be seen from the news of vaccines that entered clinical trials recently. US-based biotechnology company Moderna, Inc, Inovio Pharmaceuticals, and China-based CanSino Biologics are main competitors in the race of vaccine development. Moderna, Inc leads by entering Phase-II clinical trials while casino recently received approval for initiating clinical trials.

As vaccine development in its way, its effective delivery in our physiological system is also very important. Nanotechnology-based designing of microneedle array is an upcoming area of drug delivery with a several-fold increase in potency. Microneedles consist of several projections of about 25 to 2000 um in length arranged in the form of an array on base support in the form of a patch. Microfabrication technology has the potential to revolutionize drug delivery and has successfully been demonstrated in clinical procedure includes in vitro and in vivo delivery of biomolecules. The first microneedle (MN) devices were developed using silicon but other materials like dextrin, glass, maltose, and other polymers have also been tested as per requirement. This procedure is called micromachining or micro-electromechanical systems(MEMS). Fabrication is done on thin polymeric films of the size of a contact lens, using suitable etching techniques.

Keeping in view, the upsurge of the novel SARS-CoV-2 pandemic and the subsequent demand for a lasting cure, researchers of the Pittsburgh School of Medicine, USA, and Carnegie Mellon University have jointly developed a Microneedle array that successfully delivered a COVID 19 vaccine to mice, eliciting an immune response. The vaccine PittCoVacc is delivered through microneedles on a fingertip-sized patch.

Unlike the mRNA vaccine, PittCoVacc uses synthetic fragments of the viral spike (S) protein, which is injected through the patch with about 400 dissolvable microneedles. The microneedle-based vaccine is highly scalable which an important factor in a pandemic situation is. The vaccine does not need refrigeration and maintains its potency at room temperature for a long time. Unlike traditional hypodermal vaccines, it creates transient micropores in the skin without stimulating the dermal nerves and causing pain. Microneedle-based vaccines penetrate the skin which has an abundance of cells triggering an immune response. As a result, the vaccine can be effective at much lower doses than traditional vaccines.

The curious case of our microbiome and COVID-19 pandemic

Student Contributor: SHRESTHA SENGUPTA, B.TECH Biotech Sem-IV

The novel coronavirus first isolated and identified as SARS-CoV2 from Wuhan, China responsible for respiratory-related outbreak throughout the world. The pandemic situation compelled the countries and their people into self-quarantine to prevent further spread of infection. The absence of a suitable cure with the help of available drugs and vaccines, scientists, and medical professionals around the world are racing to unravel every biological aspect of SARS-CoV2.

Now, a group of scientist especially microbiologists and genetic epidemiologists are looking at COVID-19 problems from a different perspective. Our gut is home to a complex group of microbes or microorganisms collectively known as the gut microbiota. There are approximately around 38 trillion microbes we possess in our whole body termed as the gut microbiome. Research shows the massive size of the microbiome and its diversity can play a crucial role in leading a healthy life. One area of interest related to the COVID-19 pandemic is a cordial relationship between our gut microbiome with our immune system and its response. Professor Ronald Collman, from the University of Pennsylvania, thinks that our microbiome — the bacteria and fungi that live inside our body are playing an important role in balancing the host-immune response against viral infections. Also, Professor Tim Spector from King’s College, London highlighted the role of the weak microbiome for the excessive immune response against the novel viral infections which leads to the severe acute respiratory syndrome-like situation. Constant diagnostic tests that truly recognize the presence of bacterial or fungal infections and drug-resistant pathogens play a very crucial role in the public health response to COVID-19.

The collective genome of microbes is termed as the microbiome, containalmost150 times more genes compared to the human genome. The exact relationship between the human microbiome and our immune system interactions is not yet completely understood. Microbiome analysis of COVID-19 patient and cured person utilizing the metagenomics approach can reveal the important factors responsible for the development of immunity. Earlier studies proved the role of antimicrobial peptides as major regulators of innate immunity to control pathogen growth. An in-depth analysis of those peptides identified their origin from gut microbiota and uncover their mechanism in host defense against pathogens. Antimicrobial peptide secretion, inflammasome activation, and induction for host interleukin (IL)-22, IL-17, and IL-10 production are the general strategies executed by the gut microbiota for host anti-pathogen defense. Hence, microbiome targeted therapeutics can be used to minimize the pathogen infection and also its role in the outcomes of COVID-19.

(Figure adopted from Cheng et. al. showing the role of gut microbiota plays in the induction of antimicrobial peptides expression against pathogen and subsequent immune response.)

Keeping a healthy and diverse microbiome is an important element to fight against COVID-19. Eating a wide range of fibrous food from plants enhance microbial diversity. Further presence of natural yogurt and artisan cheese in our daily diet works as a supplement of microbes (probiotics). Activation of Vitamin A in the diet plays to help to keep our immune system healthy and also in its proper regulation. The constant immunogenicity support from our healthy microbiome can prevent an overactive immune response against an incoming pathogen. It is also being observed how the microbiome diversity declines as we get aged (mostly due to the age-related changes that occur in our immune responses). That may be a reason for the higher percentage of COVID-19 cases among elders. Thus a better understanding of gut microbiota of COVID-19 patients can open a pathway for a new type of antimicrobial drugs against SARS-CoV-2.

New-age nanotechnology-based therapeutics against the virus SARS-COV-2

Student contributor: Moni Kumari, B.Sc. Biochemistry

Coronavirus disease (COVID19) is an infectious disease caused by a newly discovered coronavirus, SARS-COV-2 (Severe acute respiratory syndrome-coronavirus-2) identified in Wuhan, and responsible for Pneumonia outbreak throughout the world. This outbreak was started in China in December 2019 and become worldwide within a timeframe of a few months. World Health Organization recognized it as a pandemic on 11^th March 2020. So far, more than 2 million people around the world have been infected with this virus with an increase in the number of deaths that is being reported every day. Importantly, developed nations are more affected by a higher number of casualties.

Nanotechnology is an important area of research dealing with designing noble nanoscale particles with an application in a wide area of science. Unlike other new-generation drugs having large molecular structures, nanoparticles are so small that they can move through our body and blood circulatory systems without disrupting other functions, such as our immune system. Scientists around the world are working constantly to device new nanoparticles to address the current situation of COVID-19.

This scanning electron microscope (SEM) image shows SARS-CoV-2 (round gold objects) emerging from the surface of cells cultured in the lab. The nanoscale dimension of coronavirus was revealed in this image. (Image: NIAID-RML)

Nanoparticle diagnostic kit: Conventional diagnostic kits commercially available today for the detection of coronavirus are not very accurate and also in short of supply. Additionally. It needs the extraction of total RNA sample from the patient for detection. To overcome these problems research groups from the Norwegian University of Science and Technology (NTNU) design new iron oxide-based nanoparticles coated with silica. The iron oxide confers its magnetic properties to nanoparticles and silica coating gives it a strong affinity for RNA, the genetic material inside the virus that causes COVID-19. The new test uses the magnetic properties of nanoparticles to extract RNA from a solution containing a test sample from the patient. The solution contains substances that crack the virus open so that its genetic material can be extracted. RNA from the virus in the solution is strongly attracted to the silica-covered magnetic nanoparticles. The next step is to use a magnet to pull the RNA-covered particles out of the solution and submit it for RT-PCR. Importantly, this kit has been used successfully to test more than 1,50,000 COVID-19 patients in Norway.

Nanoparticle vaccine: Vaccine is a dead or weakened antigen that provokes our immune system to create antibodies before the body is exposed to the live viruses. Scripps research from San-Diego USA is trying to develop a nanoparticle-based platform for vaccines against coronavirus. The prototype of the vaccine possesses CoV-2 spike protein protruding from a protein nanoparticle scaffold. Thus, the nanoscale platform is going to mimic like a virus (virus-like particle) which upon vaccination can induce our immune system to rapidly generate antibodies against coronavirus, offering recipient protection against the real SARS-CoV-2 virus. The Research group has recently applied for a patent with the name of one component self-assembling protein nanoparticle (1cSApNP)vaccine.

Nanobots or Nanorobots with Theranostic properties: Researchers from Northwestern University, Illinois are trying to device more advanced nanoparticles which can possess both properties of detection and neutralization of virus particles. Theranostic is an advanced area of research of designing molecules with both diagnosis and therapeutic power. The surface of this newly designed smart nanoparticles is going to carry biological molecules (Furin peptide) that can bind coronavirus with a very high affinity and thereby detect and assemble them. The same nanoparticle can encapsulate with biological substances that can neutralize the viruses. The biological substance can be bee venom which was proven earlier in the neutralization of HIV. Biological nanoparticles are preferable in comparison to chemically synthesized particles as they have fewer side effects. Thus these smart nanoparticles can work like a nanorobots and roam around in our blood vessels while detecting and killing the pathogenic virus.