Marine environment : A source of new drug discovery

Drugs from the sea

" For a very long time , drugs from different organisms have been discovered and used to prevent a wide range of diseases. Ancient civilization used extracts of plant or animal products as drugs. In India where the ayurveda gave access to a large variety of medicines from plants reported since 1000 BC. With the passage of time, majority of the world's population extensively depends on plants for medicines. plants are the root source of most of the commercial drugs available today". But it has been later found that medicines can be obtained from many other wide ranges of organisms other than plants. Many organisms both terrestrial and aquatic organisms are able to produce several medicinal products. For the past few decades, marine microorganisms has proved to be a extensive source of  a wide variety of bioactive compounds that can acts as anti-inflammatory ,antibacterial, antifungal, and antimalarial in nature.
 

Need of new drugs 

 Due to some disadvantages of the existing drugs there has been a call for new drugs from unexplored sources. Many of the drugs have side effects that necessitate the need for new drugs. There is the necessity of exploring new cost-effective drugs as many of the existing drugs are very expensive. So, the view has been shifted to the search of organisms from the marine environment as sources of new drugs. The search for new biomedicines from microorganisms resulted in the isolation of more or less 10,000 metabolites with pharmacodynamic properties. Marine environment probably consist of almost 80% of world's plant and animal species. The sea water exihibits harsh environment that include extremities in temperature, salinity, pressure, different levels of aeration and radiation, overcoming effects of mutation, combating infections, fouling and overgrowth by other organisms. SEA WATER SERVES AS THE PROPER ENVIRONMENT FOR LIVING CELLS, SINCE IT CONTAINS MOST OF THE CHEMICAL ELEMENTS GROWTH AND MAINTANENCE OF PLANT AND ANIMAL PROTOPLASM. 

 Marine microorganisms

Marine microorganisms inhabit in all the existing niches ranging from polar ice to hydrothermal vents in the deep sea. Microbes also compete for space and nutrients in the marine environments that has lead to the production of the drugs so far and in future too. Recently, there has been an extremely developing interest for marine microorganisms because of their genetic and biochemical diversities. Microbes are present in mangrove areas as well as in oligotrophic open ocean regions.

" Much of Nature's treasure trove of small molecules remains to be unexplored, particularly from the marine and microbial environments". 

Microbes can be easily collected in considerable amounts, isolated and cultured in laboratory premises also. Microorganisms are often in mutuality or symbiotic relationships with other organisms in the marine environment like sponges, coral reefs, echinoderms etc. Microorganisms associated with marine invertebrates have reported to produce a wide range of bioactive compounds.

Marine Bacteria

Sea water contains high concentrations of bacteria. These organisms produce antibiotics to defend themselves from potentially harmful microorganisms. Marine bacteria are rich source of secondary metabolites. Marine cyanobacteria can photosynthesize and form the base level of the food chains. They have the ability to produce biologically active compounds that can induce cytotoxicity, anti-inflammatory, and antibacterial activities. They are popular anticancer agents. For example, Apratoxin produced by the species Lyngya is potentially cytotoxic to lung cancer cells in humans.

Marine Fungi

Marine fungi are prolific sources of many natural products. Compounds like cycloglobosins and halovirs have been isolated from fungi. Sorbicilactone a novel alkaloid produced from the sponge ( Ircinia fasciculata) associated fungus penicillium chrysogenum. Marine myxobacteria is also a god source of antibiotics.

" Although the number of natural products is increasing day by day, very few compounds find their way to the market because of many factors which may include cytotoxicity that they show on normal human cell lines or unfit for medical supplements".

Many research works are going on to find new medicines from the coldest and deepest places on the planet. Therefore, scientists are focusing to find new drugs from such unexplored environment to find medicines to treat diseases like AIDS and cancer. 

Drugs from the sea is an ongoing research programme to discover drugs from the marine organisms. such a result would help to identify novel compounds not only marine microorganisms but also from the other macroorganisms. It could be understood that marine microorganisms have a great potential for drugs that should be explored properly and exploited well.

  

 

Plants do also have stress, it is releaved by its tiny friend !! Guess who it is ?!

We always say " Look deep into the nature, and then you will understand everything better". Nature is more responsive for us to live peacefully. That gives us happiness whenever we look at the nature.

Plants are the most cheerful organisms that cherishes the Nature.

Plants are always smarter, you know !!! Its pretty cool, they eat sunlight and leaves out the fresh air. But when it comes to extreme environmental conditions such as drought, salinity, and freezing temperature there is adverse effect on the growth and the productivity of crop plants.

The temperature ( heat, chilling, freezing) drought and salinity stress together represent Abiotic stress. Due to increase in population, there is more demand for food and hence agricultural practise must feed more people. This increasing demand must combat with new strategies that are to be enforced to enhance crop productivity.

One feasible way to combat with stress problem is to develop crops that are more tolerant to abiotic stresses, so that the new land can be brought under cultivation. Although traditional breeding method provides marginal relief, genetic engineering offers fastest and effective strategy for dealing stresses problem particularly in enhancing plant tolerance to stress.

In nature several organisms have evolved resistant traits that enable them to survive in extreme environment. Several microorganisms have been used as a model  system to characterize stress induced genes. Generally, when plants or microorganisms are continuously exposed to extreme environmental conditions , their stress relieving genes that are transcribed might encode enzymes involved in regulating particular metabolic pathways or proteins with specific functions. Response to abiotic stresses enable the organisms to adapt to an unfavorable condition singly by altering the metabolic way.

Considering stress factors, drought and salinity are the most significant issues threatening agricultural production on a global scale. It is estimated that total economic value of loss caused by drought and heat globally is 1.3 billion and due to cold is about 18.6 billion. This has enhanced the scientific manpower to evolve transgenic strategy to enhance plant productivity. 

Ice nucleating bacteria

                   

Formation of ice on the plant cells ( outer membrane ) is a complex chemical process. The importance of ice nucleating bacteria is recognized in recent years. The occurrance of  these bacteria has been reported in most part of the plants- Cereals, fruits and vegetable crops. The ice-nucleating bacteria synthesize proteins, which coalesce with water molecules to form ice crystals at temperature around 32° F. As the ice crystals grow, they can pierce the plant cells and severely damage the plants.

Plants can be treated with copper compounds to kill the bacteria. Another approach is to use urea solution so that the ice formation is minimized.

Ice Minus Bacteria

          The bacterium Pseudomonas syringae is one of the highly prevalent ice-forming organisms in nature. With genetic manipulations, the gene that directs the synthesis of ice- related bacterial proteins in P.syringae was removed. These newly developed bacteria are reffered to as ice-minus bacteria.

It was in 1987, ice minus bacteria were sprayed on to the field of potato plants and strawberry plants. Another strain of P.syringae  commercially labelled as Frostban was later developed and used in crop fields.

It may be noted here ice-minus bacteria of P.syringae was the first transgenic bacteria that were used outside the laboratory. Fortunately, the experiments yielded encouraging results, since crop damage due to the frost formation was found to be reduced.

Arabidopsis with cold tolerant genes 

Scientists were successful in developing cold-tolerant genes ( around 20) in Arabidopsis when these plants were gradually exposed to slowly declining temperatures.They are also identified a coordinating gene that encodes a protein, which acts as a transcription factor for regulating the expression of cold-tolerant genes. By introducing the coordinating gene, expression of cold-tolerant genes was triggered, and this protected the plants against cold temperature. More work is in progress in this direction. 

References

https://en.wikipedia.org/wiki/Arabidopsis_thaliana

https://www.nature.com/subjects/plant-stress-responses 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3252258/ 

https://en.wikipedia.org/wiki/Abiotic_stress 

https://www.livescience.com/54517-ice-nucleating-bacteria-explained.html 

https://microbewiki.kenyon.edu/index.php/Bacterial_nucleation_in_pseudomonas_syringae 

Save your DNA for future Generations

DNA in the diagnosis of Genetic diseases

Traditional laboratory tests for the diagnosis of genetic diseases are mostly based on the estimation of metabolites and/ or enzymes. This is usually done after the onset of symptoms. 

The laboratory test based on DNA analysis can specifically diagnose the inherited diseases at the genetic level. DNA based tests are useful to discover, well in advance , whether the individuals or their offsprings are at risk for any genetic disease. Further, such tests can also be employed for the prenatal diagnosis of hereditary diseases.

By knowing the genetic basis of the diseases, the individuals can be advised on how to limit the transmission of the disease to their offsprings. It may also be possible , in due course of time, to treat genetic diseases by appropriate gene therapies.

Theoretically, it is possible to develop screening tests for all single gene diseases, some of the genetic diseases like cystic fibrosis, sickle-cell anemia, Duchenne's muscular dystrophy, Huntington's disease, Fragile X syndrome, Alzheimer's disease, Amyotrophic lateral sclerosis, Cancers, Diabetes, Deafness, Glaucoma, Baldness, Parkinson's disease, Hemochromatosis, Menke's disease etc.,

A Novel concept of Gene Bank

As the search continues by scientists for the identification of more and more genes responsible for various diseases, the enlightened public, is very keen to enjoy the fruits of this research outcome. As of now, DNA probes are available for a large number of genetically predisposed disorders.

Gene banks are the centres for the storage of individual's DNAs for the future use to diagnose diseases. For this purpose, the DNA isolated from a person's cells( usually white blood cells) is stored. As and when a DNA probe for the detection of a specific disease is available, the stored DNA can be used for the diagnosis or risk assessment of the said genetic disease.

Infact, some institutions have established gene banks. They store the DNA samples of the interested customers at a fee( one firm was charging 200 dollars) for a specific period ( say around 20-25 years). For the risk assessment of any disease,  it is advisable to have the DNAs from close relatives of atleast 2-3 generations.

The collection of DNA fragments ( specifically genes) from a particular species represents gene libraries. The creation or construction of gene libraries is accomplished by isolating the complete genome which is cut into fragments , and  cloned in suitable vectors. Then the specific clone carrying the desired( target) DNA can be identified, isolated and characterized. In this manner,  a library of genes or clones (appropriately considered as gene bank)  for an entire genome of a species can be constructed.

Biotechnologists are particularly interested in the isolation of genes which encode for proteins.
Gene banks exist to conserve the genetic diversity of wild and domesticated organisms that humans depend on for food, fiber, medicine and energy.

Over 7 million plant germplasm accessions are housed in 1750 national and international gene banks. Most accessions are poorly characterized; few are ever used.

Grand challenges of DNA Bank

1. Population and income growth
2.  Land and water resources
3. climate change
4. Nutrition, Health, Biosafety
5. Sustainability

 References

 https://en.wikipedia.org/wiki/Gene_bank

http://www.agriinfo.in/default.aspx?page=topic&superid=3&topicid=2116 

http://b4fa.org/bioscience-in-brief/plantbreeding/gene-bank/ 

Do you ever thought about your childrens as the specimens to be improved?

"Sometimes, we think why some people have high IQ and high intelligence are important in improving the society. Some might think can it happen when we change Genetic qualities of an individually."

Actually, Eugenics played a important role in these idea when social scientists thought about the nation's economic reasons. They thought Only healthy persons are fit to live in this society and diseased are not

Eugenics

Eugenics is the science of improving human race based on Genetics. Improving the traits of plants and animals through breeding programmes has been in practice for centuries.

Eugenics is highly controversial subject due to social, ethical and political reasons. The proponents of eugenics argue that people with desirable and good traits ( Good blood) should reproduce while those with undesirable characters ( bad blood ) should not. The advocates of Eugenics, however, do not force any policy, but they try to convince the people to perform their duty voluntarily. The objective of eugenics is to limit the production of people who are unfit to live in the society.

 System of Arranged marriages

Galton in Hereditary Genius (1869), proposed the system of Arranged marriages , between the men of distinction and women of wealth would eventually produce the gifted race. In 1865, the basic laws of heredity were discovered by the father of modern genetics, Gregor mendel . During the early 1990s , eugenics become a scientific study pursued by both biologists and social scientists. They sought to determine the extent to which human characteristics of social importance were inherited.

 

 

Eugenics in Nazi Germany

Germany developed its own eugenic programme during 1930s. A law on eugenic sterilization was passed in 1933. In a span of three years, compulsory sterilization was done on about 250,000 people, who allegdly suffered from hereditary disabilities, feeble mindedness, epilepsy, Schizophrenia, blindness, physical deformities, and drug or alcohol addiction.

The German Government commited many attrocities in the name of racial purity. Other countries, however do not support this kind of eugenics.

Antieugenics sentiment

Eugenics was dropped from organization and Publication names. The U.S department of health, education and welfare proposed guidelines encouraging each state to repeal their respective sterilization laws. Other countries, most notably china , continued to support Eugenics directed  programs openly in order to ensure the Genetic makeup of their future.

Let's see how humans are playing with the nature and what are the outcomes if eugenic research on humans continue one day.

A Photograph showing eugenic family

 

Say thanks to your Telomerase if you look younger than your age naturally!!!

Did you know that people who look younger than their age also live a longer and healthy life that those who look older than their years ? It's true!

You already know that your cells reproduce by dividing in two. From the moment of conception until the final minutes of life, the trillions of cells in your body are regenerating through this process. Over the course of your early years, your cells continue to divide at will with little change in overall health and longevity. This is how the growth process unfolds: Your body is constantly rebuilding, repairing and renewing itself.

The prestigious journal Nature published a groundbreaking article in 1990 that introduced the world to an explanation of the genetic mechanism that involves something called the "Telomere". 

Telomeres and Telomerase

Telomeres are the special structures that prevent the continous loss of DNA at the end of the chromosomes during the course of replication and telomerase is the enzyme that adds the telomeric repeats to the end of your DNA . Telomere is also your biological clock. Each time your cells divide, a small end portion of the telomere is not copied making your telomeres shorter and shorter overtime.
https://www.tasciences.com/what-is-a-telomere/ 

As they shorten with each new division, they cause the chromosomes to fold differently exposing a diffrernt portion of your genome.This is how you can be so different at 72 than you were at 2. This process eventually signals to your cells to "grow old" and stop dividing and that cell line dies off.

Nutritional affects to grow younger

A growing body of research is showing that  certain Nutrients play a huge role in protecting or even increasing, telomere length, thereby affecting longevity.

Researches also found that women who use vitamin b12 supplements have longer telomeres than those who don't. Vitamin D3, Zinc , iron, omega-3 fatty acids, and vitamin C and E also influence telomere length. 

Top 12 anti-aging nutrients

1. Vitamin D
2. Astaxanthin
3. Ubiquinol ( CoQ10)
4.  Fermented foods/probiotics
5. Krill Oil
6. Vitamin K2
7. Magnesium
8. Polyphenols ( Grapes, Cacao, Green tea)
9. Folate ( aka Vitamin B9, Or Folic acid)
10. Vitamin B12
11. Curcumin ( Turmeric)
12. Vitamin A

https://foodandnutrition.org/blogs/stone-soup/protecting-telomeres-right-food/ 

 

https://www.livestrong.com/article/506649-foods-that-boost-telomeres-telomerase/ 

Telomerase as a useful target in cancer fighting

Telomerase was a relevant factor that distinguishes cancer from normal cells. It appeared that its expression and activity is not only limited to cancer cells however, but in this particular cells, the telomerase is much more adundant. Thus, it has become a very-promising target for an anti-cancer therapy. Telomerase is one of the crucial factor to study in oder to improve the cancer diagnostics and therapy or prevention.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3370415/

https://www.sciencedaily.com/releases/2017/04/170403083123.htm

https://www.fitnessmagazine.com/weight-loss/plans/anti-aging/the-best-anti-aging-foods/ 

https://www.livestrong.com/slideshow/545202-20-anti-aging-foods/ 

 

 

Researches States the Present status of DNA Vaccines As New Generation Vaccines

Not yet a Reality!

 Vaccination is the phenomenon of preventive immunization. In the modern concept, the administration (injection or oral) of antigen to elicit an antibody response that will protect the organism against future infections. "It took nearly 100 years for the scientist to clearly understand the basis of small pox immunity."

We now know that cowpox viruses (vaccinia) inoculated by Jenner, stimulate the body's immune system to produce antibodies which neutralize the cowpox as well as small pox viruses. The present day vaccines which are more refined work in a similar fashion.

Many communicable diseases ( small pox, cholera, typhoid, tuberculosis, poliomyelitis) have been brought under the control through vaccination. However, as on today, for several diseases, there are no vaccines e.g., AIDS, leprosy, filariasis.

Recombinant DNA technology in recent years, has become a boon to produce new generation vaccines. It has very stringent regulatory requirements to use in humans, these are first tried in animals, and it may take some more years before most of them are approved for use in humans.

"India is the fourth country ( after USA, France and Belgium) in the world to develop an indigenous hepatitis B vaccine. It was launched in 1997, and is now being used."  Biotechnologists have been successful in inserting hepatitis B gene into tomato plant. These genetically engineered plants produce hepatitis B antigens. The day may not be far off to get immunized against hepatitis B by having a tomato with Lunch!

Genetic Immunization 

The immune response in the body was stimulated by DNA molecule. Genetic immunization by using a DNA vaccines is a novel approach that came into being in 1990. By screening the DNA fragments of the pathogenic genome, it is possible to choose one or few DNA vaccines that can offer maximal immune protection.

Edible plant DNA vaccines serve as a cheap and safe production systems. The first clinical trials in humans, using a plant-derived vaccine were conducted in 1997. This involved the ingestion of transgenic potatoes with a toxin of E.coli causing diarrhea. Some success was reported.

The fate of the DNA vaccine in the host cells is not yet clear. There is a possibility of this DNA getting integrated into the host genome and this may interrupt the normal functions. There also exists a danger of cancer due to DNA vaccines.

Potato is also used as a vechicle foe cholera vaccine. A group workers have developed a gene altered potato containing attenuated cholera vaccine. These potatoes when fed to mice induced immunity against cholera.

Importance of Vaccines

Vaccine primes the body to attack an infecting pathogen. The body develops immunity. Infectious diseases are prevented. Certain diseases are treated. Eg. Diptheria, tetanus etc. Snake bite is treated . Small pox, polio, etc. are eradicated from humans by vaccines. No need for booster dose.

  References

https://en.wikipedia.org/wiki/DNA_vaccination 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3202319/ 

https://www.medscape.com/viewarticle/715527_8 

https://www.omicsonline.org/open-access/dna-vaccines-how-much-have-we-accomplished-in-the-last-25-years-2157-7560-1000283.php?aid=55732 

 

Here is the Mini Testing device Lab on your hand for the Early diagnosis of cancer!!

 Molecular messengers between cells

Birth, life and death involve the integration of complex array of biosignals that living cells sense and process to respond to adopt the modifications of their environment.

The signals sent and received by the cells during their whole existence are essential for the harmonious development of tissues, organs and bodies. They also control movement, thought and behavior.

Dysfunctioning of these cell networks is associated with pathological situations that can range from abnormal proliferations to death.

Deciphering the molecular basis for the coordinated treatment biological signals is a challenge. It will provide better insight into the processes controlling biological activities such as growth , differentiation and quiesence. It will also open the road for new therapies in order to fight with diseases resulting from improper signalling.

Numerous studies have permitted to decipher the various steps of signal transduction, i.e. the propagation of chemical signals, from the outside of the cell to the nucleus and establish their critical function in the maintenance of normal cell behavior. Because of their key role in the control of normal life, and because alterations of the signal transduction pathways have been associated to the development of many types of pathologies including cancer, these processes have been the subject of thousands of publication.

Lab-on-a-chip

Yong Zeng, assistant professor of chemistry at the University of Kansas and his fellow researchers developed the lab-on-a-chip initially for early detection of lung cancer- the number-one cancer killer in the U.S.

Lung cancer is currently detected mostly with an invasive biopsy, after tumors are larger than 3 centimeters in diameter and even metastatic. 

" Using the lab-on-chip, lung cancer could be detected much earlier, using only a drop of a patients's blood, according to Zeng."

Developing blood-based tests is appealing for non-invasive disease diagnosis, especially when biopsy is difficult, costly, and sometimes not even an option. Tumour- derived exosomes have attracted increasing interest in non-invasive cancer diagnosis and monitoring of treatment response.

A new microfluidic approach was developed to streamline and expedite the exosome analysis pipeline by integrating specific immunoisolation and targeted protein analysis of circulating exosomes. 

This technique provides a general platform to detect tumour-derived exosomes for cancer diagnosis. The device is made up of widely used silicone rubber called polydimethylsiloxane and uses a technique called "on- chip-immunoisolation".

We can foresee that the microfluidic exosome analysis platform will form the basis of  critically needed infrastructure for advancing the biology and clinical utilization of exosomes.

References

 https://www.cancer.gov/about-cancer/diagnosis-staging/diagnosis

https://tmrresearchblog.com/increased-government-initiatives-propel-exosome-diagnostic-therapeutic-market/ 

https://biosignaling.biomedcentral.com/articles/10.1186/1478-811X-1-3 

https://www.cancer.net/navigating-cancer-care/diagnosing-cancer/tests-and-procedures 

https://www.mayoclinic.org/diseases-conditions/cancer/in-depth/cancer-diagnosis/art-20046459