Caenorhabditis elegans is a tiny, free-living nematode found worldwide. Newly hatched larvae are 0.25 millimeters long and adults are 1 millimeter long. Their small size means that the animals are usually observed with either dissecting microscopes, which generally allow up to 100X magnification, or compound microscopes, which allow up to 1000X magnification. Because C. elegans is transparent, individual cells and subcellular details are easily visualized using Nomarski (differential interference contrast, DIC) optics.
C. elegans has a rapid life cycle and exists primarily as a self-fertilizing hermaphrodite, although males arise at a frequency of <0.2%. These features have helped to make C. elegans a powerful model of choice for eukaryotic genetic studies. In addition, because the animal has an invariant numbers of somatic cells, researchers have been able to track the fate of every cell between fertilization and adulthood in live animals and to generate a complete cell lineage. Researchers have also reconstructed the shape of all C. elegans cells from electron micrographs, including each of the 302 neurons of the adult hermaphrodite. Moreover, because of the invariant wild-type cell lineage and neuroanatomy of C. elegans, mutations that give rise to developmental and behavioral defects are readily identified in genetic screens. Finally, because C. elegans was the first multicellular organism with a complete genome sequence, forward and reverse genetics have led to the molecular identification of many key genes in developmental and cell biological processes.
The experimental strengths and the similarities between the cellular and molecular processes present in C. elegans and other animals across evolutionary time (metabolism, organelle structure and function, gene regulation, protein biology, etc.) have made C. elegans an excellent organism with which to study general metazoan biology. At least 38% of the C. elegans protein-coding genes have predicted orthologs in the human genome, 60-80% of human genes have an ortholog in the C. elegans genome, and 40% of genes known to be associated with human diseases have clear orthologs in the C. elegans genome. Thus, many discoveries in C. elegans have relevance to the study of human health and disease.
Genomics C elegan genome and model organismiqraakbar8
The C. elegans genome is about 100 million base pairs long and consists of six pairs of chromosomes in hermaphrodites or five pairs of autosomes with XO chromosome in male C. elegans and a mitochondrial genome. The genome contains an estimated 20,470 protein-coding genes.
In 1963, Sydney Brenner introduced Caenorhabditis elegans as a model organism for pursuing research in developmental biology and neurology.It is a free-living, non-parasitic soil nematode that can be safely used in the laboratory and is common around the world.
This ppt gives an idea of general anatomy of this small creature,its life cylce,study as a model organism and its importance in the study of ageing.
Genomics C elegan genome and model organismiqraakbar8
The C. elegans genome is about 100 million base pairs long and consists of six pairs of chromosomes in hermaphrodites or five pairs of autosomes with XO chromosome in male C. elegans and a mitochondrial genome. The genome contains an estimated 20,470 protein-coding genes.
In 1963, Sydney Brenner introduced Caenorhabditis elegans as a model organism for pursuing research in developmental biology and neurology.It is a free-living, non-parasitic soil nematode that can be safely used in the laboratory and is common around the world.
This ppt gives an idea of general anatomy of this small creature,its life cylce,study as a model organism and its importance in the study of ageing.
hox genes and its role in development both in human and drosophila . homeotic genes. homeobox genes. developmental biology. different types of homeotic genes in drosophila and human. deficiencydiseases due to lack of hox genes in human
Caenorhabditis elegans is a tiny, free-living nematode found worldwide. Newly hatched larvae are 0.25 millimetres long and adults are 1 millimetre long. Their small size means that the animals are usually observed with either dissecting microscopes, which generally allow up to 100X magnification, or compound microscopes, which allow up to 1000X magnification. Because C. elegans is transparent, individual cells and subcellular details are easily visualized using Nomarski (differential interference contrast, DIC) optics.
C. elegans has a rapid life cycle and exists primarily as a self-fertilizing hermaphrodite, although males arise at a frequency of <0.2%. These features have helped to make C. elegans a powerful model of choice for eukaryotic genetic studies. In addition, because the animal has an invariant number of somatic cells, researchers have been able to track the fate of every cell between fertilization and adulthood in live animals and to generate a complete cell lineage. Researchers have also reconstructed the shape of all C. elegans cells from electron micrographs, including each of the 302 neurons of the adult hermaphrodite. Moreover, because of the invariant wild-type cell lineage and neuroanatomy of C. elegans, mutations that give rise to developmental and behavioural defects are readily identified in genetic screens. Finally, because C. elegans was the first multicellular organism with a complete genome sequence, forward and reverse genetics have led to the molecular identification of many key genes in developmental and cell biological processes.
The experimental strengths and the similarities between the cellular and molecular processes present in C. elegans and other animals across evolutionary time (metabolism, organelle structure and function, gene regulation, protein biology, etc.) have made C. elegans an excellent organism with which to study general metazoan biology. At least 38% of the C. elegans protein-coding genes have predicted orthologs in the human genome, 60-80% of human genes have an ortholog in the C. elegans genome, and 40% of genes known to be associated with human diseases have clear orthologs in the C. elegans genome. Thus, many discoveries in C. elegans have relevance to the study of human health and disease.
Fixed Action Pattern (FAP) is a series or sequence of acts that occur behaviorally in animals. it is also known as instinctive behaviour as it is determined by gene of an organism and exhibited automatically without having any prior experience.
Introduction
About Drosophila
Genome of Drosophila
Life cycle
Differentiation
Development of Drosophila
* Embryonic development
* Dorsal -ventral and
* Anterior posterior development
* Body segmentation
* Homeotic gene
Conclusion
Reference
INTRODUCTION
ABOUT DROSOPHILA
PHYSICAL APPEARANCE
CELL BIOLOGY OF DROSOPHILA DEVELOPMENT
LIFE CYCLE
THE DROSOPHILA GENOME
UNUSAL FEATURES OF DROSOPHILA
SEX DETERMINATION
GENETIC MARKERS
DEVELOPMENT IN DROSOPHILA
CLEAVAGE
THE ORIGINS OF ANTERIOR-POSTERIOR POLORITY {GENES}
CHROMOSOME ABERRATIONS
CONCLUSIONS
REFERENCES
Mr. Rakesh Sharma. M, M.Sc., in Applied Microbiology, Research Assistant with seven years of experience in Central Inter- Disciplinary Research Facility (CIDRF), SBV - Puducherry has joined as Research Associate in Mahatma Gandhi Medical Preclinical Research Centre (MGMPRC). A talk by him on “Zebrafish as an animal model for biomedical research” is scheduled on 19th November, 2022 (Saturday) at 2.30 pm in A1 conference hall, 1st floor Hospital block, MGMCRI.”
hox genes and its role in development both in human and drosophila . homeotic genes. homeobox genes. developmental biology. different types of homeotic genes in drosophila and human. deficiencydiseases due to lack of hox genes in human
Caenorhabditis elegans is a tiny, free-living nematode found worldwide. Newly hatched larvae are 0.25 millimetres long and adults are 1 millimetre long. Their small size means that the animals are usually observed with either dissecting microscopes, which generally allow up to 100X magnification, or compound microscopes, which allow up to 1000X magnification. Because C. elegans is transparent, individual cells and subcellular details are easily visualized using Nomarski (differential interference contrast, DIC) optics.
C. elegans has a rapid life cycle and exists primarily as a self-fertilizing hermaphrodite, although males arise at a frequency of <0.2%. These features have helped to make C. elegans a powerful model of choice for eukaryotic genetic studies. In addition, because the animal has an invariant number of somatic cells, researchers have been able to track the fate of every cell between fertilization and adulthood in live animals and to generate a complete cell lineage. Researchers have also reconstructed the shape of all C. elegans cells from electron micrographs, including each of the 302 neurons of the adult hermaphrodite. Moreover, because of the invariant wild-type cell lineage and neuroanatomy of C. elegans, mutations that give rise to developmental and behavioural defects are readily identified in genetic screens. Finally, because C. elegans was the first multicellular organism with a complete genome sequence, forward and reverse genetics have led to the molecular identification of many key genes in developmental and cell biological processes.
The experimental strengths and the similarities between the cellular and molecular processes present in C. elegans and other animals across evolutionary time (metabolism, organelle structure and function, gene regulation, protein biology, etc.) have made C. elegans an excellent organism with which to study general metazoan biology. At least 38% of the C. elegans protein-coding genes have predicted orthologs in the human genome, 60-80% of human genes have an ortholog in the C. elegans genome, and 40% of genes known to be associated with human diseases have clear orthologs in the C. elegans genome. Thus, many discoveries in C. elegans have relevance to the study of human health and disease.
Fixed Action Pattern (FAP) is a series or sequence of acts that occur behaviorally in animals. it is also known as instinctive behaviour as it is determined by gene of an organism and exhibited automatically without having any prior experience.
Introduction
About Drosophila
Genome of Drosophila
Life cycle
Differentiation
Development of Drosophila
* Embryonic development
* Dorsal -ventral and
* Anterior posterior development
* Body segmentation
* Homeotic gene
Conclusion
Reference
INTRODUCTION
ABOUT DROSOPHILA
PHYSICAL APPEARANCE
CELL BIOLOGY OF DROSOPHILA DEVELOPMENT
LIFE CYCLE
THE DROSOPHILA GENOME
UNUSAL FEATURES OF DROSOPHILA
SEX DETERMINATION
GENETIC MARKERS
DEVELOPMENT IN DROSOPHILA
CLEAVAGE
THE ORIGINS OF ANTERIOR-POSTERIOR POLORITY {GENES}
CHROMOSOME ABERRATIONS
CONCLUSIONS
REFERENCES
Mr. Rakesh Sharma. M, M.Sc., in Applied Microbiology, Research Assistant with seven years of experience in Central Inter- Disciplinary Research Facility (CIDRF), SBV - Puducherry has joined as Research Associate in Mahatma Gandhi Medical Preclinical Research Centre (MGMPRC). A talk by him on “Zebrafish as an animal model for biomedical research” is scheduled on 19th November, 2022 (Saturday) at 2.30 pm in A1 conference hall, 1st floor Hospital block, MGMCRI.”
1 What is the study systemGeneral information. E.g. What is a .docxhoney725342
1 What is the study system?
General information. E.g. What is a “cell line”? Include images.
1 Why would a researcher use this study system?
The particular features of this system that make it useful. E.g. cell lines allow the study of genetically identical cells in many labs
1 What type of research questions can this study system be used to help answer?
List a few examples of research questions or general areas of research that can be addressed using this system. Elaborate a little on each, so we understand what you mean.
1 How does a researcher typically use this system?
What are the logistics of it? E.g. basic information about how they culture and propagate cell lines.
1 What are the pros and cons of this study system?
List and briefly explain any drawbacks or caveats that we should be aware of, along with particular benefits E.g. mammalian cell lines need adequate facilities and resources to be propagated, but they also allow for the study of mammalian cellular systems in vitro instead of studying another eukaryote like yeast.
6.Are there alternatives or variations on this study system?
If you can’t use this particular study system, what are your options for alternatives? E.g. Use yeast as a representative of a eukaryotic cell.
1 What is a real example from primary literature of this study system being used?
Provide a brief summary of the research that used the study system of interest, including the main objective, basic methods used, the main results, and conclusions. Include an image of at least one figure or table, along with an explanation of what that figure/table illustrates. You must provide the complete citation of the paper and/or a link to the online paper.
8.List of sources and places where we can find more information.
Background
C. elegans: A Simple Multicellular Model Organism
Scientists worldwide conduct basic research to address gaps in our knowledge in the hopes that this information can serve humanity in the future. Basic biological research seeks to answer questions of such elementary cellular and organismal activities as how cells grow, divide, die, move, store and use energy, and communicate.
Scientists use model organisms in basic research to answer these questions because model organisms offer simplified cellular systems that reproduce quickly, are easy to maintain, and are cost efficient. For example,
if a DNA mutation is known to result in a neurological disorder, more data can be generated using a model organism such as C. elegans, which reproduces and matures every 2–3 days, rather than waiting for a human child to mature and show symptoms. Commonly used basic model organisms include S. cerevisiae (yeast), C. elegans (nematode), D. melanogaster (fruit fly), and M. musculus (mouse).
Despite the seeming lack of a relationship to human beings, these model organisms have helped researchers understand the basic cellular machinery underlying a host of human pathologies such as cancer, neurological disorders, ...
With the DNA sequences of more than 90 genomes completed, as well as a draft sequence of the human genome, a major challenge in modern biology is to understand the expression, function, and regulation of the entire set of proteins encoded by an organism—the aims of the new field of proteomics. This information will be invaluable for understanding how complex biological processes occur at a molecular level, how they differ in various cell types, and how they are altered in disease states. The term proteomics describes the study and characterization of a complete set of proteins present in a cell, organ, or organism at a given time.
In general, proteomic approaches can be used (a) for proteome profiling, (b) for comparative expression analysis of two or more protein samples, (c) for the localization and identification of posttranslational modifications, and (d) for the study of protein-protein interactions. The human genome harbours 26000–31000 protein-encoding genes; whereas the total number of human protein products, including splice variants and essential posttranslational modifications (PTMs), has been estimated to be close to one million. It is evident that most of the functional information on the genes resides in the proteome, which is the sum of multiple dynamic processes that include protein phosphorylation, protein trafficking, localization, and protein-protein interactions. Moreover, the proteomes of mammalian cells, tissues, and body fluids are complex and display a wide dynamic range of proteins concentration one cell can contain between one and more than 100000 copies of a single protein.
A rapidly emerging set of key technologies is making it possible to identify large numbers of proteins in a mixture or complex, to map their interactions in a cellular context, and to analyze their biological activities. Mass spectrometry has evolved into a versatile tool for examining the simultaneous expression of more than 1000 proteins and the identification and mapping of posttranslational modifications. High-throughput methods performed in an array format have enabled large-scale projects for the characterization of protein localization, protein-protein interactions, and the biochemical analysis of protein function. Finally, the plethora of data generated in the last few years has led to approaches for the integration of diverse data sets that greatly enhance our understanding of both individual protein function and elaborate biological processes.
Fungi get their nutrition by absorbing organic compounds from the environment. Fungi are heterotrophic: they rely solely on carbon obtained from other organisms for their metabolism and nutrition. Fungi have evolved in a way that allows many of them to use a large variety of organic substrates for growth, including simple compounds such as nitrate, ammonia, acetate, or ethanol. Their mode of nutrition defines the role of fungi in their environment.
Fungi obtain nutrients in three different ways:
They decompose dead organic matter. A saprotroph is an organism that obtains its nutrients from non-living organic matter, usually dead and decaying plant or animal matter, by absorbing soluble organic compounds. Saprotrophic fungi play very important roles as recyclers in ecosystem energy flow and biogeochemical cycles. Saprophytic fungi, such as shiitake (Lentinula edodes) and oyster mushrooms (Pleurotus ostreatus), decompose dead plant and animal tissue by releasing enzymes from hyphal tips. In this way, they recycle organic materials back into the surrounding environment. Because of these abilities, fungi are the primary decomposers in forests.
They feed on living hosts. As parasites, fungi live in or on other organisms and get their nutrients from their host. Parasitic fungi use enzymes to break down living tissue, which may cause illness in the host. Disease-causing fungi are parasitic. Recall that parasitism is a type of symbiotic relationship between organisms of different species in which one, the parasite, benefits from a close association with the other, the host, which is harmed.
They live mutualistically with other organisms. Mutualistic fungi live harmlessly with other living organisms. Recall that mutualism is an interaction between individuals of two different species, in which both individuals benefit.
The invertebrates, or invertebrates, are animals that do not contain bony structures, such as the cranium and vertebrae. The simplest of all the invertebrates are the Parazoans, which include only the phylum Porifera: the sponges.
Parazoans (“beside animals”) do not display tissue-level organization, although they do have specialized cells that perform specific functions. Sponge larvae are able to swim; however, adults are non-motile and spend their life attached to a substratum.
Since water is vital to sponges for excretion, feeding, and gas exchange, their body structure facilitates the movement of water through the sponge. Structures such as canals, chambers, and cavities enable water to move through the sponge to nearly all body cells.
An enzyme attracts substrates to its active site, catalyzes the chemical reaction by which products are formed, and then allows the products to dissociate (separate from the enzyme surface). The combination formed by an enzyme and its substrates is called the enzyme–substrate complex. When two substrates and one enzyme are involved, the complex is called a ternary complex; one substrate and one enzyme are called a binary complex. The substrates are attracted to the active site by electrostatic and hydrophobic forces, which are called noncovalent bonds because they are physical attractions and not chemical bonds.
An endangered species is a species that is very likely to become extinct in the near future, either worldwide or in a particular political jurisdiction. Endangered species may be at risk due to factors such as habitat loss, poaching and invasive species. The International Union for Conservation of Nature (IUCN) Red List lists the global conservation status of many species, and various other agencies assess the status of species within particular areas. Many nations have laws that protect conservation-reliant species which, for example, forbid hunting, restrict land development, or create protected areas. Some endangered species are the target of extensive conservation efforts such as captive breeding and habitat restoration.
The hydrogens in methane practically do not exhibit acidic character. However when two of the hydrogens are replaced
by electron withdrawing groups, the rest of the hydrogens become acidic in nature. The electron withdrawing groups
present on both sides attract the electron towards themselves and thus weaken the –CH bond of methylene. Thus
hydrogen atom can dissociate to give a stable anion. This same phenomena applies to EAA, the two hydrogen atoms
bonded to methylene group become acidic and reactive due to two electron withdrawing functional groups i.e. acetyl
and ester attached o methylene carbon.
Thus methylene group attached to two electron withdrawing functional groups is termed as reactive methylene group
Sterilization is the complete removal of microorganisms from an object or surfaces.
Sterilization is obtained when microorganisms are subjected to antimicrobial agents for
sufficient time and at optimum conditions.
Sterilization is a process of eradicating live microorganisms from substances. It is done to
preserve things for a long time and kill germs. If something is not sterilized, it may cause
infection to those who use it. Therefore, it should not be taken for granted.
High-altitude adaptation in humans is an instance of evolutionary modification in certain human populations, including those of Tibet in Asia, the Andes of the Americas, and Ethiopia in Africa, who have acquired the ability to survive at altitudes above 2,500 meters. This adaptation means irreversible, long-term physiological responses to high-altitude environments, associated with heritable behavioural and genetic changes. While the rest of the human population would suffer serious health consequences, the indigenous inhabitants of these regions thrive well in the highest parts of the world. These people have undergone extensive physiological and genetic changes, particularly in the regulatory systems of oxygen respiration and blood circulation, when compared to the general lowland population.
Around 81.6 million people, approximately 1.1% of the world's human population, live permanently at altitudes above 2,500 metres (8,200 ft)[4] putting these populations at risk for chronic mountain sickness (CMS). However, the high-altitude populations in South America, East Africa, and South Asia have done so for millennia without apparent complications. This special adaptation is now recognised as an example of natural selection in action. The adaptation of the Tibetans is the fastest known example of human evolution, as it is estimated to have occurred any time around 1,000 B.C.E. to 7,000 B.C.E.
The voltage clamp is an experimental method used by electrophysiologists to measure the ion currents through the membranes of excitable cells, such as neurons while holding the membrane voltage at a set level. A basic voltage-clamp will iteratively measure the membrane potential, and then change the membrane potential (voltage) to the desired value by adding the necessary current. This "clamps" the cell membrane at a desired constant voltage, allowing the voltage clamp to record what currents are delivered. Because the currents applied to the cell must be equal to (and opposite in charge to) the current going across the cell membrane at the set voltage, the recorded currents indicate how the cell reacts to changes in membrane potential. Cell membranes of excitable cells contain many different kinds of ion channels, some of which are voltage-gated. The voltage clamp allows the membrane voltage to be manipulated independently of the ionic currents, allowing the current-voltage relationships of membrane channels to be studied.
Yogurt is a diary product widely used by the present generation in their daily diets. you probably don't give much thought to buying yogurt in the store. You have your favorite brand, or maybe you like trying new varieties each week; either way, you just grab it and go.
It is easy to take yogurt for granted, but this delicious dairy product has a long and storied history that started way before the convenience of commercialized yogurt. Read on to discover its surprising origins in ancient civilizations and how it started being mass-produced.
Yogurts are fermented dairy products obtained from lactic acid fermentation by two species of lactic acid bacteria, that is, Streptococcus thermophilus and Lactobacillus delbrueckii subsp. bulgaricus. This fermentation leads to acidification and milk coagulation, without addition of rennet (as in cheese), and allows an increase of the shelf life as a result of the low pH. world. They involve probiotic bacteria, which are defined according to the FAO/WHO in 2011 as ‘live microorganisms that, when administered in adequate amounts, confer a health benefit on the host.’
Exonucleases are enzymes that work by cleaving nucleotides one at a time from the end (exo) of a polynucleotide chain. A hydrolyzing reaction that breaks phosphodiester bonds at either the 3′ or the 5′ end occurs. Its close relative is the endonuclease, which cleaves phosphodiester bonds in the middle (endo) of a polynucleotide chain. Eukaryotes and prokaryotes have three types of exonucleases involved in the normal turnover of mRNA: 5′ to 3′ exonuclease (Xrn1), which is a dependent decapping protein; 3′ to 5′ exonuclease, an independent protein; and poly(A)-specific 3′ to 5′ exonuclease.
A diffusion-limited enzyme catalyses a reaction so efficiently that the rate limiting step is that of substrate diffusion into the active site, or product diffusion out. This is also known as kinetic perfection or catalytic perfection. Since the rate of catalysis of such enzymes is set by the diffusion-controlled reaction, it therefore represents an intrinsic, physical constraint on evolution (a maximum peak height in the fitness landscape). Diffusion limited perfect enzymes are very rare. Most enzymes catalyse their reactions to a rate that is 1,000-10,000 times slower than this limit. This is due to both the chemical limitations of difficult reactions, and the evolutionary limitations that such high reaction rates do not confer any extra fitness.
Cancer is an abnormal growth of cells caused by multiple changes in gene expression leading to
dysregulated balance of cell proliferation and cell death and ultimately evolving into a population
of cells that can invade tissues and metastasize to distant sites, causing significant morbidity and,
if untreated, death of the host.
It is characterized by alterations in the expression of multiple genes, leading to dysregulation of the normal cellular program for cell division and cell differentiation. This results in an imbalance of cell replication and cell death that favours the growth of a tumour cell population. Tumour is an abnormal lump or growth of cells. When the cells in the tumour are normal, it is benign. If something goes wrong, and they overgrew and produced a lump, the cells are abnormal and can grow uncontrollably, they are cancerous cells, and the tumour is malignant. Benign tumour won't invade nearby tissues or spread to other areas of the body (metastasize). A benign tumour is less
worrisome unless it is pressing on nearby tissues, nerves, or blood vessels and causing damage.
Fibroids in the uterus or lipomas are examples of benign tumours. Malignant means that the tumour is made of cancer cells, and it can invade nearby tissues. Some cancer cells can move into the bloodstream or lymph nodes, where they can spread to other tissues within the body—this is called metastasis. Cancer can occur anywhere in the body including the breast, intestines, lungs,
reproductive organs, blood, and skin. The occurrence of cancer varies in different organs (Fig: 01)
Clinically, cancer appears to be many different diseases with different phenotypic characteristics.
As cancerous growth progresses, genetic drift in the cell population produces cell heterogeneity in such characteristics as cell antigenicity, invasiveness, metastatic potential, rate of cell proliferation, differentiation state, and response to chemotherapeutic agents. At the molecular
level, all cancers have several things in common, which suggests that the ultimate biochemical
lesions leading to malignant transformation and progression can be produced by a common but
not an identical pattern of alterations of gene readout. In general, malignant cancers cause significant
morbidity and will be lethal to the host if not treated
The immune system has evolved to protect the host from a universe of pathogenic microbes that are themselves constantly evolving. The immune system also helps the host eliminate toxic or allergenic substances that enter our body. It is a host defence system comprising many biological structures and processes within an organism that protects against disease. To function properly, an immune system must detect a wide variety of agents, known as pathogens, from viruses to parasitic worms, and distinguish them from the organism's own healthy tissue. The host uses both innate and adaptive mechanisms to detect and eliminate pathogenic foreign bodies. Both of these mechanisms include self-nonself discrimination.
The main parts of the immune system are:
• White Blood Cells
• Antibodies
• Complement System
• Lymphatic System
• Spleen
• Bone Marrow
• Thymus.
The immune system has evolved to protect the host from a universe of pathogenic microbes that are themselves constantly evolving. The immune system also helps the host eliminate toxic or allergenic substances that enter our body. It is a host defence system comprising many biological structures and processes within an organism that protects against disease. To function properly, an immune system must detect a wide variety of agents, known as pathogens, from viruses to parasitic worms, and distinguish them from the organism's own healthy tissue. The host uses both innate and adaptive mechanisms to detect and eliminate pathogenic foreign bodies. Both of these mechanisms include self-nonself discrimination.
The main parts of the immune system are:
• White Blood Cells
• Antibodies
• Complement System
• Lymphatic System
• Spleen
• Bone Marrow
• Thymus.
DNA Amplification is a Ubiquitous Mechanism of Oncogene Activation in Lung an...Shryli Shreekar
Chromosomal translocation is the best-characterized
genetic mechanism for oncogene activation. However, there
are documented examples of activation by alternate
mechanisms, for example gene dosage increase, though
its prevalence is unclear. Here, we answered the fundamental question of the contribution of DNA amplification
as a molecular mechanism driving oncogenesis. Comparing
104 cancer lines representing diverse tissue origins
identified genes residing in amplification ‘hotspots’ and
discovered an unexpected frequency of genes activated by
this mechanism. The 3431 amplicons identified represent
B10 per hematological and B36 per epithelial cancer
genome. Many recurrently amplified oncogenes were
previously known to be activated only by disease-specific
translocations. The 135 hotspots identified contain 538
unique genes and are enriched for proliferation, apoptosis
and linage-dependency genes, reflecting functions advantageous to tumor growth. Integrating gene dosage with
expression data validated the downstream impact of the
novel amplification events in both cell lines and clinical
samples. For example, multiple downstream components of
the EGFR-family-signaling pathway, including CDK5,
AKT1 and SHC1, are overexpressed as a direct result of
gene amplification in lung cancer. Our findings suggest that
amplification is far more common a mechanism of
oncogene activation than previously believed and that
specific regions of the genome are hotspots of amplification.
THE IMPORTANCE OF MARTIAN ATMOSPHERE SAMPLE RETURN.Sérgio Sacani
The return of a sample of near-surface atmosphere from Mars would facilitate answers to several first-order science questions surrounding the formation and evolution of the planet. One of the important aspects of terrestrial planet formation in general is the role that primary atmospheres played in influencing the chemistry and structure of the planets and their antecedents. Studies of the martian atmosphere can be used to investigate the role of a primary atmosphere in its history. Atmosphere samples would also inform our understanding of the near-surface chemistry of the planet, and ultimately the prospects for life. High-precision isotopic analyses of constituent gases are needed to address these questions, requiring that the analyses are made on returned samples rather than in situ.
Richard's entangled aventures in wonderlandRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
Richard's aventures in two entangled wonderlandsRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
Nutraceutical market, scope and growth: Herbal drug technologyLokesh Patil
As consumer awareness of health and wellness rises, the nutraceutical market—which includes goods like functional meals, drinks, and dietary supplements that provide health advantages beyond basic nutrition—is growing significantly. As healthcare expenses rise, the population ages, and people want natural and preventative health solutions more and more, this industry is increasing quickly. Further driving market expansion are product formulation innovations and the use of cutting-edge technology for customized nutrition. With its worldwide reach, the nutraceutical industry is expected to keep growing and provide significant chances for research and investment in a number of categories, including vitamins, minerals, probiotics, and herbal supplements.
Multi-source connectivity as the driver of solar wind variability in the heli...Sérgio Sacani
The ambient solar wind that flls the heliosphere originates from multiple
sources in the solar corona and is highly structured. It is often described
as high-speed, relatively homogeneous, plasma streams from coronal
holes and slow-speed, highly variable, streams whose source regions are
under debate. A key goal of ESA/NASA’s Solar Orbiter mission is to identify
solar wind sources and understand what drives the complexity seen in the
heliosphere. By combining magnetic feld modelling and spectroscopic
techniques with high-resolution observations and measurements, we show
that the solar wind variability detected in situ by Solar Orbiter in March
2022 is driven by spatio-temporal changes in the magnetic connectivity to
multiple sources in the solar atmosphere. The magnetic feld footpoints
connected to the spacecraft moved from the boundaries of a coronal hole
to one active region (12961) and then across to another region (12957). This
is refected in the in situ measurements, which show the transition from fast
to highly Alfvénic then to slow solar wind that is disrupted by the arrival of
a coronal mass ejection. Our results describe solar wind variability at 0.5 au
but are applicable to near-Earth observatories.
1. Caenorhabditis elegans
“A Transparent Window into Biology”
Guided by,
Ms. Sanjana Shajan
Guest Faculty
Dept. Molecular Biology,
Yuvaraja's College (Autonomous),
Mysuru
Presented by,
SHRYLI K S
VIIIth Semester
YMB17118 Molecular
Biology, Yuvaraja's
College (Autonomous),
Mysuru
11 June, 2021
2. Contents
Classification
History
Basic Introduction
Life Cycle
Genetics and Genomics
Why C. elegans?
Epidermis: a model for extracellular matrix production, wound healing, and cell fusion
Muscles—a model for controlling animal movement
The digestive system—a model for organogenesis and pathogenesis
The nervous system—a model for neurobiology
Reproductive tissue—a model for sex-specific anatomy
Key Discoveries
Conclusion
References
3. Classification
The binomial name fo C. elegans was first given in 1900, by Émile Maupas a French librarian, zoologist and
botanist.
Kingdom: Animalia
Phylum: Nematoda
Class: Chromadorea
Order: Rhabditida
Family: Rhabditidae
Genus: Caenorhabditis
Species: C. elegans
History
In the 1970s, Sydney Brenner and his students sought an organism wherein it might be possible to identify
each gene involved in development as well as to trace the lineage of each and every cell. Nematode
roundworms seemed like a good group to start with because embryologists such as Richard Goldschmidt
and Theodor Boveri had already shown that several nematode species have a relatively small number of
chromosomes and a small number of cells with invariant cell lineages. Brenner and his colleagues
eventually settled on C. elegans, a small (1 mm long), free-living (i.e., nonparasitic) soil nematode with
relatively few cell types. In Brenner's original vision, detailed elucidation of the development and anatomy
of C. elegans would serve as the foundation for the subsequent analysis of mutants. Both of these efforts
were completed primarily at the LMB (Laboratory of Molecular Biology) Cambridge. The transparency of
the animal allowed John Sulston, Robert Horvitz, Judith Kimble, David Hirsh, and Einhard Schierenberg to
describe every cell division starting with the single-celled zygote and ending with the adult male and
hermaphrodite. These efforts produced the first and only entire cell lineage of any multicellular organism.
During this same time, John White, Sydney Brenner, Donna Albertson, Eileen Southgate, Sam Ward, and
Nichol Thomson described the anatomy and connectivity of all 302 neurons of the adult hermaphrodite.
These projects set a standard for completeness in the understanding of the animal that has been a hallmark
of C. elegans research. Sydney Brenner, Robert Horvitz, and John Sulston were awarded the 2002 Nobel
Prize in Physiology or Medicine in part for the significance of the lineage project as a platform for
discovery of genes that orchestrated developmental decisions.
Introduction
Caenorhabditis elegans is a tiny, free-living nematode found worldwide. Newly hatched larvae are 0.25
millimeters long and adults are 1 millimeter long. Their small size means that the animals are usually
observed with either dissecting microscopes, which generally allow up to 100X magnification, or
compound microscopes, which allow up to 1000X magnification. Because C. elegans is transparent,
individual cells and subcellular details are easily visualized using Nomarski (differential interference
contrast, DIC) optics.
C. elegans has a rapid life cycle and exists primarily as a self-fertilizing hermaphrodite, although males
arise at a frequency of <0.2%. These features have helped to make C. elegans a powerful model of choice for
Fig 01: Émile Maupas
4. eukaryotic genetic studies. In addition, because the animal has an invariant numbers of somatic cells,
researchers have been able to track the fate of every cell between fertilization and adulthood in live animals
and to generate a complete cell lineage. Researchers have also reconstructed the shape of all C. elegans cells
from electron micrographs, including each of the 302 neurons of the adult hermaphrodite. Moreover,
because of the invariant wild-type cell lineage and neuroanatomy of C. elegans, mutations that give rise to
developmental and behavioral defects are readily identified in genetic screens. Finally, because C.
elegans was the first multicellular organism with a complete genome sequence, forward and reverse
genetics have led to the molecular identification of many key genes in developmental and cell biological
processes.
The experimental strengths and the similarities between the cellular and molecular processes present in C.
elegans and other animals across evolutionary time (metabolism, organelle structure and function, gene
regulation, protein biology, etc.) have made C. elegans an excellent organism with which to study general
metazoan biology. At least 38% of the C. elegans protein-coding genes have predicted orthologs in the
human genome, 60-80% of human genes have an ortholog in the C. elegans genome, and 40% of genes
known to be associated with human diseases have clear orthologs in the C. elegans genome. Thus, many
discoveries in C. elegans have relevance to the study of human health and disease.
Anatomy
Similar to other nematodes, C. elegans has an unsegmented, cylindrical body shape that is tapered at the
ends. It shows the typical nematode body plan with an outer tube and an inner tube separated from each
other by the pseudocoelomic space. The outer tube (body wall) consists of cuticle, hypodermis, excretory
system, neurons and muscles, and the inner tube, the pharynx, intestine and, in the adult, gonad. All of
these tissues are under an internal hydrostatic pressure, regulated by an osmoregulatory system
Life cycle
C. elegans embryogenesis takes approximately 16 hours at 20° (all of the subsequent times are also for
development at 20°). A virtually impermeable eggshell is made after fertilization, allowing the embryo to
develop completely independent of the mother. However, embryos are usually retained within the
hermaphrodite until about the 24-cell stage at which time they are laid. The hermaphrodite embryo hatches
with 558 nuclei (some nuclei are in multi-nuclear syncytia, so the cell count is lower) and becomes a first
Fig 02: C. elegans anatomy. Major anatomical
features of a hermaphrodite (A) and male (B)
viewed laterally. (A) The dorsal nerve cord
(DNC) and ventral nerve cord (VNC) run
along the entire length of the animal from
the nerve ring. Two of the four quadrants of
body wall muscles are shown. (B) The
nervous system and muscles are omitted in
this view, more clearly revealing the
pharynx and intestine. (C) Cross-section
through the anterior region of the C.
elegans hermaphrodite (location marked with
a black line in A) showing the four muscle
quadrants surrounded by the epidermis and
cuticle with the intestine and gonad housed
within the pseudocoelomic cavity.
5. stage (L1) larva (PAR-3, PAR-6, PKC-3, PAR-1, PAR-2, SKN-1, PAL-1, PIE-1, MED-1, MED-2, POP-1, TCF,
(pha-4) and muscles (hlh-1), MOM-2, MOM-5, GLP-1 and APX-1). The animals begin to eat and develop
through four larval stages (L1-L4). The L1 stage is ~16 hr long; the other stages are ~12 hr long. Each stage
ends with a sleep-like period of inactivity called lethargus in which a new cuticle (outer collagenous layer)
is made. Lethargus ends with the molting of the old cuticle. Approximately 12 hr after the L4 molt, adult
hermaphrodites begin producing progeny for a period of 2-3 days until they have utilized all of their self-
produced sperm; additional progeny can be generated if the sperm-depleted hermaphrodite mates with a
male. After the reproductive period, hermaphrodites can live several more weeks before dying of
senescence.
When bacteria are depleted and the animals are crowded, L2 larvae activate an alternative life cycle and
molt into an alternative L3 larval stage called the “dauer” larva (“dauer” in German means “lasting"; the
signal is actually processed by L1 animals, but its results are not seen until the so-called “L2d” stage). The
dauer larva cuticle completely surrounds the animal and plugs the mouth preventing the animal from
eating and thereby arresting development. The dauer cuticle has enhanced resistance to chemicals, so it
provides the dauer with greater protection against environmental stresses and caustic agents. Dauer larvae
can survive for many months and are the dispersal form most commonly encountered in the wild. When
the dauer larvae are transferred onto plates with bacteria, they shed their mouth plugs, molt, and continue
their development as slightly different L4 larvae.
Life span regulating genes: DAF-2, AGE-1, DAF-16, math-33, JNK-1, CST-1, HSF-1, SKN-1 and PQM-1.
Genetics and Genomics
A major reason Sydney Brenner chose to study C. elegans was the ease of genetic manipulation. C. elegans
is a well-established and powerful genetic system. Self-fertilization means that after hermaphrodites (P0s)
are mutagenized, any mutant alleles (except dominant lethals) can be maintained through self-propagation
in first-generation (F1) progeny, second-generation (F2) progeny, etc. without mating. This property makes
obtaining these progeny easy. A second genetic advantage of C. elegans is that it grows quickly. Since
animals take ~3 days at 25° (~3.5 days at 20°) to develop from fertilized eggs to adults producing their own
fertilized eggs, mutant homozygotes can be detected two generations (~1 week) after mutagenesis. In
addition, the ability to freeze and recover C. elegans makes it possible to preserve mutant strains without
Fig 06: Life Cycle of C. elegans
6. worrying that they have acquired unwanted suppressors, other modifiers, or additional background
mutations or have lost important mutations, particularly if they are maintained as heterozygotes.
Therefore, much less effort needs to be devoted to strain maintenance.
The use of genetics in C. elegans is in forward genetics reverse genetics and Mutant-like phenotypes can
also be obtained using RNA interference (RNAi), the use of double-stranded RNA (dsRNA) to reduce gene
activity.
C. elegans was the first multicellular eukaryotic organism to have its genome sequenced. The entire C.
elegans genome is 100 Mb and has 20,444 protein-coding genes. Both C. elegans sexes contain five autosomal
chromosomes named linkage group (LG ) I, II, III, IV, and V and the X chromosome. Compared to
vertebrate genes, C. elegans genes are relatively small with the average gene size of 3 kb due primarily to
the presence of very small introns. The chromosomes do not contain traditional centromeres; during
mitosis the microtubule spindle attaches to more than one position along the chromosome.
Why choose C. elegans?
Sharing large amounts of genetic and cellular information has been central to the success of C.
elegans research. In addition to being a powerful system for genetic studies, C. elegans has many inherent
advantages as a model for eukaryotic biology. These features include its small size, large brood size, ease of
cultivation, low maintenance expense, long-term cryopreservation, quick generation time, transparency,
invariant cell number and development, and the ability to reduce gene activity using feeding RNAi.
Although not usually mentioned, another favorable feature of C. elegans is the organisms are quite benign
to humans. In fact, because they cannot grow at body temperatures, they cannot grow in humans. Some
nematodes, e.g., Ascaris suum, induce a debilitating allergic reaction and must be studied in ventilated
hoods. As far as we are aware, allergic reactions to C. elegans have not been documented.
Studies of cell and developmental biology that use C. elegans are greatly aided by the transparency of the
animal, which allows researchers to examine development and changes due to mutations or altered
environments at the level of a single, identified cell within the context of the entire living organism. Thus,
many biological problems can be studied “in miniature” at the single-cell level, instead of large numbers of
cells in heterogeneous tissues. Transparency also enables a wealth of studies in living animals utilizing
fluorescent protein reporters. By labelling cells and proteins in living cells, fluorescent proteins enable
genetic screens to identify mutants defective in various cellular processes. In addition, fluorescent protein-
based reporters, which fluoresce in response to calcium flux, provide neuron-specific detection of calcium
flux under a fluorescent microscope, and therefore allow researchers to measure electrophysiological
activity in vivo. Furthermore, mapping of cell-cell and synaptic contacts can be accomplished by expressing
complementary fragments of GFP in different cells. Transparency also means that optogenetic tools, which
alter the activity of individual neurons, are particularly effective in C. elegans. In all of these experiments,
greater control of the animal's position and environment can be accomplished by microfluidic devices in
which individual worms are mounted in custom-designed channels allowing the application of various
compounds or other agents while simultaneously monitoring fluorescent readout of gene regulation or
electrophysiological activity by microscopy.
1. Epidermis: a model for extracellular matrix production, wound healing, and cell fusion
The outer epithelial layer, the epidermis, of the embryo undergoes a series of cell fusions to make large
multinucleate, or syncytial, epidermal cells. These cells secrete the cuticle, a protective layer of specialized
extracellular matrix (ECM) consisting primarily of collagen, lipids, and glycoproteins. The cuticle
determines the shape of the body and, through connection from the epidermis to muscle, provides
7. anchoring points for muscle contraction. The cuticle also serves as a model for ECM formation and function
with molecules and pathways involved in cuticle biogenesis conserved in vertebrates.
Mutations in several genes needed for cuticle formation produce visible phenotypes. Mutations in
collagen genes can result in animals that move in a corkscrew fashion [the Roller (Rol) phenotype] or that
have normal width but reduced length [the Dumpy (Dpy) phenotype]. Other mutations affect the struts
formed between layers of the adult cuticle, resulting in fluid-filled blisters [the Blister (Bli) phenotype]. Still
other mutations make the animals longer than normal [the Long (Lon) phenotype]. At the end of each
larval stage, C. elegans sheds its cuticle and secretes a new one to accommodate the growing organism.
Genes involved in cuticle formation are regulated so that the cuticle is re-established after each molt.
Studying the epidermis has led to insights in early cell movements, wound healing, cell-cell fusions, and
the establishment of epithelial layers in developing embryos. As the “skin” of C. elegans, the epidermis is a
model for the innate immune response to pathogens and for repair after a physical wound such as a needle
puncture. The wounded epidermis upregulates both Ca++ signalling to direct actin polymerization for
repair and innate immune signalling pathways to help promote survival after injury. The cell-cell fusion
events leading to the multinucleate epidermis and genes important for this process have been studied. This
work has supported the idea that repression of fusion in some cells may be just as important for proper
development as activation of cell fusion in other cells.
2. Muscles—a model for controlling animal movement
Just interior and connected to the epidermis are four quadrants (95 cells) of body-wall muscles that run
along the length of the body. The regular contraction and relaxation of the muscle cells leads to the
“elegant” sinusoidal movement of the animal. These somatic muscles are striated (although, unusually,
they are obliquely striated) and mononucleate (muscle cells do not fuse as they do in vertebrates) with
multiple sarcomeres per cell.
Genetic studies of muscle led to the first cloning and sequencing of a myosin gene (unc-54), and this
finding provided major insights into the structure of all myosins. unc-54 and many
other unc (uncoordinated) genes encoding proteins needed for muscle activity produce a “floppy
paralytic” phenotype. The study of the assembly of sarcomeres into functional muscles and, in particular,
the proteins mediating attachment to the plasma membrane has revealed many molecules in common with
vertebrate focal adhesion complexes. Genetic screens designed to understand molecules involved in muscle
contraction have also led to insights regarding muscle-wasting diseases such as Duchenne's Muscular
Dystrophy and cardiomyopathies. In addition to the body-wall muscle, C. elegans has muscles that control
eating (pharyngeal muscles), egg-laying (vulval and uterine muscles and the contractile gonad sheath),
mating (male-specific tail muscles), and defecation (enteric muscles).
3. The digestive system—a model for organogenesis and pathogenesis
Food (bacteria) enters the anterior of the animals and passes through the pharynx, a two-lobed
neuromuscular pump that grinds the food before it is passed on to the intestine for digestion. The pumping
behavior of the animals depends on the availability and the quality of the food; for example, animals pump
more when hungry and less when full. Studying pharyngeal development has been a model for
organogenesis, including how epithelial morphogenesis and cell-fate specification occur during
development. For example, the transcription factor PHA-4 plays a major regulatory role in the organ
identity of the pharynx. Animals defective in PHA-4 function do not contain a pharynx and embryos that
overexpress PHA-4 have more pharyngeal cells. The vertebrate FoxA transcription factors are homologous
8. to PHA-4 and are involved in gut development in many species. Intestinal development has been studied
in detail. C. elegans has served as a model to study infection and response to infection by several different
bacterial pathogens, microsporidia, and viruses that colonize the digestive system.
4. The nervous system—a model for neurobiology
C. elegans has become an important model for the study of neurobiological questions. Researchers have
identified genes and mechanisms needed for neuronal generation and specification, cell death, precursor
migration, synapse formation, chemosensory and mechanosensory transduction, neuronal degeneration,
neurite regeneration, and glial function. Researchers also have investigated a variety of behaviors, both
simple and complex, including chemotaxis, thermotaxis, several responses to touch, male-specific mating
rituals, social feeding, and both associative and non-associative learning. C. elegans also experiences periods
of restful inactivity that are similar to aspects of mammalian sleep.
The nervous system of the adult hermaphrodite has 302 neurons; that of the adult male has 383 neurons.
The majority of neuronal cell bodies are arranged in a few ganglia in the head, in the ventral cord, and in
the tail (the specialized male tail has the majority of the extra neurons). In addition to neurons, C.
elegans has several glia-like support cells, which are primarily associated with sensory neurons, but are not
as numerous as in vertebrates.
C. elegans neurons make more than 7000 chemical synapses and gap junction connections. Chemical
synapses are identified in electron micrographs by presynaptic darkening and synaptic vesicles;
postsynaptic specializations are not obvious. C. elegans uses many of the most common neurotransmitters,
including acetylcholine, glutamate, γ-amino butyric acid (GABA), dopamine, and serotonin and has several
receptors for their detection. In addition to the chemical synaptic and gap junction connections, C.
elegans neurons are modulated by numerous neuroendocrine signals. From the perspective of cellular and
molecular detail, most of the problems of neurobiology can be studied in the worm.
In C. elegans, some individual neurons perform functions that would be performed by multiple neurons in
vertebrates. For example, individual olfactory neurons express multiple G protein-coupled odorant
receptors, rather than a single receptor as in vertebrates; each of the two mirror image bilateral ASE
chemosensory cells respond to several different ions; and the connectivity of the touch receptor neurons
suggests that their stimulation initiates several different activities. Thus, functions of multiple vertebrate
sensory neurons are compressed into a single neuron in C. elegans.
5. Reproductive tissue—a model for sex-specific anatomy
The C. elegans sexes display several obvious anatomical differences in the somatic gonad, secondary sexual
structures, and body size. The somatic gonad is located in the center of the body alongside the intestine. In
hermaphrodites the gonad consists of two mirror-image U-shaped tubes; in males the gonad consists of a
single U-shaped lobe. Both gonads house the germline where the oocytes and sperm develop. The somatic
gonad and the germline develop together during larval stages until animals reach maturity at the young
adult stage. A powerful advantage for studies of the C. elegans germline is that one can observe all stages of
meiosis at once as the germline is a visible gradient of development. Studying the germline has been a
model for meiosis, gamete development, fertilization, stem cell biology, and even tumor formation.
Secondary sexual mating structures are the vulva in hermaphrodites and the fan-shaped tail in males. The
vulva develops in the center of the epidermis on the ventral side of the hermaphrodite and is the conduit
for sperm entry from the male and egg laying from the uterus. Studying vulval morphogenesis has
9. provided insights into signaling by the Notch, EGF, and Wnt pathways that coordinate the spatiotemporal
development of the organ. Defects in these pathways can lead to animals with no vulva [the egg-laying
defective (Egl) phenotype] or with many vulval-like protrusions [the multivulva (Muv) phenotype]. In
many cases these animals cannot lay eggs (or mate), and their progeny develop internally, hatch within the
hermaphrodite, and create the “bag-of-worms” phenotype whereby the larvae consume the mother (a
process called endotokia matricidia). This phenotype, which also occurs when wild-type adult
hermaphrodites are starved, has been used to identify numerous egg-laying defective mutants. For
example, details of Ras GTPase/Map Kinase signaling have been elucidated through the identification of
mutants in enhancer/suppressor screens of vulval phenotypes.
Key Discoveries
C. elegans has been used as a model organism in major research areas including but not limited to
developmental biology, neurobiology, cell biology, and aging. The worm has contributed decisively to our
understanding of fundamental cellular and developmental processes including cell signaling, programmed
cell death, neuronal and synaptic properties and function, muscle biology, and sex determination.
Similarly, C. elegans has contributed enormously to our understanding of human neurodegenerative
disorders, cancer, and aging. Indeed, C. elegans has also emerged as a powerful experimental system to
study the molecular and cellular aspects of human disease in vivo. It has been estimated that about 42% of
the human disease genes have an ortholog in the genome of C. elegans including those genes associated
with Alzheimer’s disease, juvenile Parkinson’s disease, spinal muscular atrophy, hereditary non-polyposis
colon cancer, and many other age-related disorders. Modeling a human disease in a simple invertebrate,
such as C. elegans, allows the dissection of complex molecular pathways into their component parts and
thus provides meaningful insight into the pathogenesis of a complex disease phenotype. Notable examples
are:
Year Discovery References
1974 Identification of mutations that affect animal behavior Brenner 1974; Dusenberry et al. 1975; Hart 2006
1975 First description of mutations that affect thermotaxis and
mechanotransduction
Hedgecock and Russell 1975; Sulston et al. 1975; Chalfie and
Sulston 1981; Mori and Ohshima 1995,
1977 First cloning and sequencing of a myosin gene Macleod et al. 1977
1977 Genetic pathways for sex determination and dosage
compensation described
Hodgkin and Brenner 1977; Meyer 2005; Zarkower 2006
1981 Identification of mutations affecting touch sensitivity Sulston et al. 1975; Chalfie and Sulston 1981
1981 First germline stem cell niche identified Kimble and White 1981; Kimble and Crittenden 2005
1983 Notch signaling, presenilins, ternary complex, and lateral
inhibition roles in development described
Greenwald et al. 1983; Levitan and Greenwald
1995; Petcherski and Kimble 2000; Greenwald and Kovall
2012
1983 First complete metazoan cell lineage Sulston and Horvitz 1977; Kimble and Hirsh 1979; Sulston et
al. 1983
1983 Discovery of apoptosis (cell death) genes Hedgecock et al. 1983; Ellis and Horvitz 1986; Yuan and
Horvitz 1992; Yuan et al. 1993; Conradt and Xue 2005
1984 Identification of heterochronic genes Ambros and Horvitz 1984; Slack and Ruvkun 1997
1986 First complete wiring diagram of a nervous system White et al. 1986; Jarrell et al. 2012; White 2013
1987 Discovery of the first axon guidance genes Hedgecock et al. 1987, 1990; Culotti 1994
1987 Identification of role of Notch signaling in embryonic
blastomeres
Priess et al. 1987; Priess 2005
1988 Discovery of par genes, whose products affect the
asymmetric distribution of cellular components in
embryos
Kemphues et al. 1988; Gönczy and Rose 2005
1988 Identification of the first LIM and POU homeodomain
transcription factors
Way and Chalfie 1988; Finney et al. 1988; Hobert 2013
1990 First description of a role for RAS signaling function in Beitel et al. 1990; Han and Sternberg 1990; Sternberg
10. metazoan development 2005; Sundaram 2013
1993 Demonstration of a role for insulin pathway genes in
regulating lifespan
Friedman and Johnson 1988; Kenyon et al. 1993; Kimura et
al. 1997; Collins et al. 2007
1993 Identification of genes for conserved synaptic functions Gengyo-Ando et al. 1993; Richmond et al. 1999; Richmond
2007
1993 First microRNA (lin-4) and its mRNA target (lin-
14) described
Lee et al. 1993; Wightman et al. 1993 Vella and Slack 2005
1993 Identification of nonsense-mediated decay genes Pulak and Anderson 1993; Hodgkin 2005b
1994 Introduction of GFP as a biological marker Chalfie et al. 1994; Boulin et al. 2006
1994 First demonstration of specific olfactory receptor/ligand
pair
Sengupta et al. 1994; Bargmann 2006
1998 First metazoan genome sequenced C. elegans Sequencing Consortium 1998; Schwarz 2005
1998 Discovery of RNA interference (RNAi) Fire et al. 1998
2000 Conservation and ubiquity of miRNAs Pasquinelli et al. 2000
2000 Development of genome-wide RNAi screening/first full
genome-wide profiling of gene function
Fraser et al. 2000; Kamath et al. 2001
2000 Transgenerational inheritance and its mediation by piRNA Grishok et al. 2000; Ashe et al. 2012
2002 First cytoplasmic polyA polymerase (gld-2) discovered Wang et al. 2002; Kimble and Crittenden 2005
2005 First full-genome RNAi profiling of early embryogenesis Sönnichsen et al. 2005
2005 First use of channelrhodopsin optogenetics in an intact
animal
Nagel et al. 2005
2011 Discovery of first nematode viruses Félix et al., 2011
Conclusion
It all started when in 1963, Sydney Brenner sent a letter to Max Perutz, the chairman of the Medical
Research Council's Laboratory of Molecular Biology (LMB), detailing his concerns that the “classical
problems of molecular biology have either been solved or will be solved in the next decade” and proposing
that the future of molecular biology lies in the extension to other fields, “notably development and the
nervous system”. With the simplicity and power of prokaryotic genetics in mind, he proposed that a
nematode (round worm), Caenorhabditis briggsae, would be an ideal system in which to tackle these
problems. Later, he settled on the related nematode C. elegans as the focus of his efforts because
the elegans strain grew better than the briggsae isolate in Brenner's laboratory.
Since work on C. elegans genetics began in earnest during the 1970s, this animal has proven fruitful for
making general discoveries about cell and developmental biology. These findings have helped us
understand molecular genetic mechanisms in all animals. Evolution has maintained thousands of
conserved genes that play similar, or in some cases nearly identical, functions in nematodes and other
animals including humans. For example, the vertebrate apoptosis regulator Bcl-2 can functionally
substitute for its C. elegans ortholog ced-9. Thus, discoveries with direct relevance to understanding all
animals were made possible by what initially appeared to be an ambitious and esoteric undertaking to
define in detail the structure and genetics of an apparently simple animal. Today, C. elegans is actively
studied in over a thousand laboratories worldwide with over 1500 C. elegans research articles published
each year for the last 5 years.
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Apendix
• PAR- Partition defective protein
• Unc: Uncoordinated
• PKC: Protein Kinase C
• SKN: Skinhead Protein. Controls the fate of the EMS blastomere, the cell that generates the posterior
pharynx.
• PAL: Phenylalanine ammonia lyase (PAL) is a key enzyme of the phenylpropanoid pathway that
catalyzes the deamination of phenylalanine to trans-cinnamic acid, a precursor for the lignin and
flavonoid biosynthetic pathways.
• PIE: Pharynx and Intestine in Excess. Maternally provided PIE-1 is required for germline cell fate
determination. Functions as a repressor of RNA polymerase II-dependent gene expression in the
developing germline. Required for expression of nos-2 in P4 germline blastomere cells. Inhibits the
histone deacetylase activity of hda-1. Represses transcriptional activation of cdk-9 and cit-1.1, which
are members of the P-TEFb complex.
• MED: Mesoderm and Endoderm Determination. Enables sequence-specific DNA binding activity. Is
involved in endodermal cell fate specification and pharynx development. Located in nucleus.
• POP: POsterior Pharynx. Enables several functions, including RNA polymerase II transcription
factor binding activity; beta-catenin binding activity; and enzyme binding activity. Is involved in
several processes, including mesodermal cell fate commitment; mitochondrial unfolded protein
response; and regulation of transcription, DNA-templated.
• TCF: T-cell factor/lymphoid enhancer factor (TCF/LEF). TCF/LEFs are multifunctional proteins
that use their sequence-specific DNA-binding and context-dependent interactions to specify
which genes will be regulated by Wnts.
• HLH: Helix-loop-helix. Regulates numerous developmental events in eukaryotic cells.
• MOM: Mom protein. Required in embryonic development for endoderm specification and the
correct positioning and orientation of the mitotic spindles and division planes in blastomere cells.
Involved in cleavage axis determination.
• GLP: Germ Line Proliferation. Enables RNA polymerase II transcription factor binding activity and
transcription coactivator activity. Is involved in several processes, including maintenance of dauer;
pharyngeal muscle development; and positive regulation of cell population proliferation. Located in
cytoplasm; endomembrane system; and lateral plasma membrane. Is spanning component of
plasma membrane. Part of RNA polymerase II transcription regulator complex. Is expressed in
several structures, including AB lineage cell; anus; germ line; neurons; and somatic nervous system.
Is an ortholog of human NOTCH1 (notch receptor 1); NOTCH2 (notch receptor 2); and NOTCH3
(notch receptor 3).
• APX: Anterior Pharynx in eXcess. Is involved in several processes, including embryonic pattern
specification; lateral inhibition; and regulation of vulval development. Is expressed in several
structures, including P6.paa; P6.pap; P6.ppa; non-striated muscle; and vulva. Is an ortholog of
human DLK2 (delta like non-canonical Notch ligand 2) and DLL3 (delta like canonical Notch ligand
3).
• DAF: abnormal DAuer Formation. Enables several functions, including 14-3-3 protein binding
activity; DNA-binding transcription factor activity; and enzyme binding activity. Is involved in
13. several processes, including defense response to other organism; regulation of dauer larval
development; and regulation of transcription, DNA-templated. Is expressed in several structures,
including gonad; hypodermis; neurons; somatic cell; and ventral nerve cord. Is an ortholog of
human FOXO1 (forkhead box O1); FOXO3 (forkhead box O3); and FOXO4 (forkhead box O4).
• AGE: Aging alteration. Is predicted to enable 1-phosphatidylinositol-3-kinase activity. Is involved
in several processes, including dauer entry; insulin receptor signaling pathway involved in
determination of adult lifespan; and regulation of synaptic growth at neuromuscular junction. Is
expressed in amphid neurons; hypodermis; and pharyngeal-intestinal valve. Is an ortholog of
human PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) and
PIK3CD (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta)
• MATH: Meprin-associated Traf homology. Encodes deubiquitylase, suppresses the extended
lifespan.
• JNK: c-Jun N-terminal kinases. JNKs (c-Jun N-terminal kinases) are a group of mitogen-activated
protein kinases (MAPKs), originally called stress activated protein kinases (SAPKs), because they
are activated by various environmental stresses.
• CST: Caenorhabditis STE20-like kinase. Enables protein serine/threonine kinase activity. Is
involved in determination of adult lifespan and muscle fiber development. Is expressed in
hypodermis; sensory neurons; terminal bulb; and vulva. Is an ortholog of human STK3
(serine/threonine kinase 3).
• HSF: Heat Shock Factor. Enables calmodulin binding activity; promoter-specific chromatin binding
activity; and sequence-specific double-stranded DNA binding activity. Is involved in several
processes, including dauer larval development; defense response to other organism; and
determination of adult lifespan. Located in nuclear stress granule. Is expressed in several structures,
including body wall musculature; hypodermis; intestine; neurons; and somatic cell. Is an ortholog
of human HSF2 (heat shock transcription factor 2).
• PQM: ParaQuat (Methylviologen) responsive. Is involved in defense response to Gram-negative
bacterium; determination of adult lifespan; and innate immune response. Is expressed in head
muscle; head neurons; intestinal cell; and pseudocoelom.
• COVID: This C. elegans line expresses the human ACE2 (angiotensin-converting enzyme 2) receptor
fused with GFP under a ubiquitous promoter. Upon treatment with Spike protein, the ACE2
receptor translocates from the cell surface to cytoplasmic vesicles.
• Limitations: Simple body plan, and lack many defined organs/tissues including a brain, blood, a
defined fat cell, internal organs, and is evolutionarily distant from humans.
• C. elegans lack certain anatomical features of mammals, including a blood transport system, a blood-
brain barrier, a first-pass metabolism process in the liver, and blood filtration in the kidney, which
may be specific for certain signal pathways or epigenetic effects.
• As a model system to predict human research outcomes, the lack of DNA methylation, an
epigenetic tag that possibly has a greater function in mammals than in nematodes, is another
limitation of C. elegans.
• Forward genetics seeks to find the genetic basis of a phenotype or trait, reverse genetics seeks to
find what phenotypes arise as a result of particular genetic sequences
• DNA methylation is essential for silencing retroviral elements, regulating tissue-specific gene
expression, genomic imprinting, and X chromosome inactivation. Importantly, DNA methylation in
different genomic regions may exert different influences on gene activities based on the underlying
genetic sequence.
• C elegans relies solely on its innate immune system to defend itself against pathogens. Studies of the
nematode response to infection with various fungal and bacterial pathogens have revealed that the
innate immune system of C. elegans employs evolutionary conserved signalling pathways.
14. • ATP8: The P-type adenosinetriphosphatases (P-type ATPases) are a family of proteins which use
the free energy of ATP hydrolysis to drive uphill transport of ions across membranes.
• A homologous gene is a gene inherited in two species by a common ancestor. Orthologous genes
are homologous gene, where the gene diverges after a speciation event. Main function is conserved.