Some significant work done in the CCMB in recent years.

CENTRE FOR CELLULAR & MOLECULAR BIOLOGY

Hyderabad 500 007 (INDIA)

CCMB is the first National Science Institute to become a co-operative member of the Indian CSICOP.

Centre for Cellular & Molecular Biology (CCMB for short) is privileged to be a constituent National Laboratory of the Council of Scientific & Industrial Research (CSIR) the premier federal-funded multidisciplinary research agency of the country which has played a crucial and pivotal role in the development of science and technology in India.

Dr. P.M.Bhargava recipient of twenty two awards and honours including Padma Bhushan, is the Director of the Centre, Lots of Research work has been conducted at the CCMB from its inception in 1976. Some of the significant work done in CCMB of human interest is explained below:

STUDIES ON EVOLUTION

The CCMB has been among the first laboratories to recognize, and draw attention to the importance of the problem of transition from the chemical to the biological evolution, in our understanding of the origin of life. A set of minimal criteria has been formulated that would have 'defined' the first 'living' cell: a critical examination of these criteria suggests that the transition could have been abrupt, possibly having occurred as a rare stochastic event. It has also been suggested that not all the information required for cellular organization may be coded for by DNA, and some support for it has been obtained in experiments on the regeneration of cell as in yeast protoplasts.

WHAT MAKE A MALE A MALE AND A FEMALE, A FEMALE?

What distinguishes us as males and females? This is, what determines our sex? This is a question we all would like to have an answer to. The mechanism by which the sex of an individual is determined has been a subject of scientific speculation since the time of Aristotle. Until 1900, it was generally thought that the sex of a human embryo is decided by environmental factors, such as maternal nutrition. Now it is known that the blueprint to produce a complete human being is carried in discrete blocks of information known as chromosomes, which are present in all cells of the body.

The genetic material in chromosomes is the chemical, DNA. There are 46 such blocks of information (or chromosomes) within a human cell; they can be arranged on the basis of their appearance under the microscope, into 23 pairs. At fertilisation, the ovum and the sperm, each of which contain 23 chromosomes - one of each pair - combine to produce the total of 46 found in the cell of the human adult. Thus 50 per cent of the genetic information is of maternal origin and 50 per cent of paternal origin.

There is one small chromosome present only in the man and not in the woman; this chromosome has been set aside by Nature to impart maleness and is called the Y chromosome. The other counterpart in the pair is the X chromosome. If the egg is fertilised by a sperm carrying the Y chromosome, the progeny would be XY, that is male; if it is fertilised by a sperm carrying an X chromosome, the progeny would by XX, that is female. A scientist in the CCMB discovered that only a small piece of DNA of a specific region of the Y chromosome, called the Bkm, is responsible for sex determination. The Bkm region was first isolated from a poisonous Indian snake, the banded Krait. When the Bkm DNA of the Y chromosome is transferred to other chromosomes, it causes females to develop as a male. The Bkm DNA, can be used in the future in diagnosing the cause of sterility in childless couples and providing genetic counselling. The technology which is being developed at the CCMB, based on its basic research in this area, would also allow one to choose the sex of the child and ensure that the child would be free of certain genetic diseases. It could also be used for sex selection in domestic animals.

GENETIC FINGERPRINTING

Work is under way to develop a new technique for identification of individual human beings through genetic fingerprinting - that is, making use of the genetic uniqueness of an individual. Each individual is unique because his genetic material, the DNA, is unique. The technique is, therefore,also called DNA fingerprinting. The major applications of such a technique would be in the establishment of paternity for personal reasons; in affiliation, wardship or divorce proceedings; and in provision to immigration authorities of clear evidence of a family relationship. The technique of DNA fingerprinting also has major application in the field of forensic science, where extremely small samples of say, blood, semen, hair roots, etc., left at the scene of a crime, may be analysed and compared with those from a person suspected of committing the crime. In the veterinary world, this technique could be used for confirmation of the pedigree of an animal.

So far, only one such technique has been developed - that is, by Dr. Alec Jeffreys of United Kingdom. This technique is being used in the UK since the last year, for purposes of identification of individuals. As it is patented. It is not available for others.

The DNA fingerprinting technique that is now being developed in the CCMB is based on a major and already widely-known discovery made by a CCMB scientist. In this discovery those parts of DNA that are involved in making a male a male and a female a female have been identified. These parts, while retaining certain common elements which make them responsible for the determination of sex and for the expression of sex-linked characteristics, have also regions which vary from individual to individual. These differences can be visualised through appropriate sophisticated techniques of molecular biology - as unique bands on an X-ray film. The technique of DNA fingerprinting being developed in the CCMB has several advantages over that of Alec Jeffreys.

MECHANISM OF CATARACT FORMATION

A very common affliction of the eye is the formation of a cataract. When cataract forms, the eye lens is no longer transparent but becomes opaque, leading to sight deficiency. What are the factors that cause the formation of cataract? This is the 'large' question that some scientists in the CCMB are attempting to answer. They have devised a method for studying the changes that happen to the intact eye lens directly, using fluorescence properties of the proteins that constitute the lens. They generate cataract in the eye lens by shining ultraviolet light or by other chemical methods, and follow the changes that happen to the transparency of the lens. An important finding has been that there exist clearing mechanisms in the lens that lead to the reduction or total avoidance of the damage (for example, by ultraviolet light) that leads to cataract. In cataractuous lens, such clearance mechanisms become inoperative. It appears that birds may not be prone to cataract as human beings are. This observation, if confirmed, may help prevent cataract in humans as well.

SEMINALPLASMIN

Semen, like blood, consists of the cellular component - the spermatozoa - and the non-cellular component, the seminal plasma. Chemical constituents of the seminal plasma are known to influence the physiological functions of spermatozoa. Studies on these constituents, specially proteins of the seminal fluid on which little work has been done so far could, therefore, be important in understanding the regulation of the function of spermatozoa - that is, their fertilising ability. Such investigations could also open up avenues for planning new strategies for regulating fertility in mammals. With these objectives in view, the CCMB has carried out extensive research on proteins of the seminal fluid and has succeeded in isolating a new protein called seminalplasmin, from bovine seminal plasma. Detailed studies on the physiological function of seminalplasmin have indicated that the protein is unique in that it has a number of interesting biological activities. For example, seminalplasmin is a potent antimicrobial agent that inhibits the growth of a variety of microorganisms. It also inhibits the motility and the fertlizing ability of mammalian spermatozoa. A critical analysis of available data indicates that the primary function of seminalplasmin may be to act as an antifertility agent. Some recent work in the CCMB has indicated that it might also be active against the AIDS Virus.

The discovery of this protein a few years ago in the CCMB, attracted world-wide attention and, as of now, well-known scientists from various parts of the world, for example, West Germany, the USA and UK, have been working on this protein.

BACTERIA AND YEASTS OF ANTARCTICA:

Bacteria and yeasts are known to be present in Antarctica, a continent which is extremely cold, dry and poor in nutrients. However, the identity of these microorganisms is not known, as also the mechanism by which they have adapted to the extreme climatic conditions of Antarctica. With this in view, microbiology of soil and water samples collected by a member of the staff of the CCMB, during the Fourth Indian Scientific Expedition to Antarctica (1984-85) have been studied in detail at the CCMB in the last three years. The centre has established the presence of bacteria and yeast in the soils and water samples collected at the Dakshin Gangotri Hill Ranges in Antarctica. Forty five pure cultures of bacteria and eight of yeast have been studied in great detail and their identity established. More than seventy five percent of the bacteria and all the yeasts, resembled species found in other continents, except that the Antarctica species are cold adapted and differ in their capacity to utilise nutrients: they thus function well at temperature of say, 10 degree C, but die at 30 degree C or above - unlike the corresponding species around us. Ten isolates of bacteria appear to be unique to Antarctica and are probably hitherto unidentified new species. (It is not very often that new species of bacteria are discovered) The molecular biology of the Antarctica bacteria and yeast is now under investigation to understand the mechanism of their adaptation to extreme cold conditions.

REGULATION OF GROWTH & MALIGNANT TRANSFORMATION

The CCMB at Hyderabad has been engaged in understanding how growth is regulated in higher organisms and what goes wrong with this regulation when a cancerous tumour is formed. For exmaple, in the liver of an adult human being, less than one in a thousand cells are dividing: most of the cells live for many months and, therefore, the need for new cells to replace the dead cells, is very small. However, if we remove a part of the liver as much as two-thirds - by surgery, most of the remaining cells begin to divide to generate new cells. And in just a few days, the original size is regained. One could ask, what is the switch that is put on that tells the cells of the liver: "Thou must now divide", and then again tells the cell to stop dividing after the original size of the liver has been regained? If the cells do not stop dividing we would have a cancer. Attempts have been on in the CCMB now for several years to understand the nature of the switch and the signal that putting on the switch conveys to the cell. A new protein has been isolated from liver which may be the key element in controlling or regulating division of cells in liver. It seems possible that cancer is a consequence of an eventual interference in the function of this protein.

WHAT DETERMINES THE TIME THAT A LIVING CELL WILL TAKE TO DIVIDE?

Work is in progress in the CCMB to understand what determines the time that a living cell will take to divide. A bacterial cell may divide in 20 minutes. Our cells may take anywhere from a few hours to more than a day. Working on a cancerous tumour of the liver, scientists at the CCMB have found two types of cells in the tumour: one which divide fast and the other which divide at a slow rate. Each of these forms can be converted genetically into the other rather easily, showing that perhaps a small number of genes - may be only one - is involved in determining the time that a cell would take to divide. (Genes, it might be recalled, are elements that control heredity.) Attempts are now being made to identify this gene and to understand precisely what function of the cell is controlled by the gene. If the gene that controls the time taken by a cell to divide can be identified, it could be used to convert slow-growing cells of commercial importance into fast growing cells by genetic engineering.

MECHANISM OF OSMOREGULATION - OR HOW LIVING ORGANISMS

COPE WITH CERTAIN KINDS OF ADVERSE ENVIRONMENT?

Work is continuing in the CCMB to find out how living organisms adapt to certain adverse circumstances. One such circumstance is a very high concentration of salts in the environment. Thus, whereas many of our cells, such as red blood cells, will disintegrate if they are placed in a solution of common salt in which the concentration of salt is more than 0.9%. However, bacteria such as E.coli, can survive merrily in an environment in which the concentration of salt may be very much higher. How are certain bacteria able to alter may be very much higher. How are certain bacteria able to alter their working machinery to allow them to survive damage by high salt concentration in the environment? The capability to do so must be written down in the genetic material - or the genes - of the bacteria. Several elements of the genetic material - that is, several genes - that are involved in regulating the response of the common bacterium, Escherichia coli, to high salt concentration in the environment, have been identified. This work has the potential of eventually helping develop plants which would be able to survive in arid or semi-arid zones. The CCMB has world leadership in this important new area.

NEW ENZYMES FROM SNAKE VENOM

Owing to their world-wide distribution, snakes are the most familiar poisonous animals. The most interesting feature of these animals, from the scientific stand point, is their venom, Snake venom is a topic of immense research by scientists all over the world, and much research work has been done on the composition of the venom, its biological effects,and the means with which it is delivered to the victim. Snake venoms contain toxic substances which effect the nerve tissues and blood cells of the prey. For the snake, the venom provides a means of self defence or of subduing the prey. It has been, however, recently realised that snake venom can also serve as a source of several enzymes. Enzymes are proteins that are present in all living organisms and serve as biological catalysts that are responsible for converting one substance into another in living systems. Two new, interesting enzymes have been isolated from the venom of cobra snakes, in the CCMB at Hyderabad. The two new enzymes degrade nucleic acids which are an important set of chemicals involved in heredity. The enzymes carry out this degradation at specific chemical bonds and can, therefore, be used to determine where such bonds are present in the molecule of the nucleic acid. No enzymes that would degrade the chemical bonds at which the two new enzymes act, are so far known. It is expected that these enzymes will find wide use as reagents for research in molecular biology and genetic engineering, and lead to development of new techniques for determining the structure of RNA (ribonucleic acid). One of the two types of nucleic acids present in all living organisms.

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Last update: 27August 1998