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The Department of Health (DOH), United Kingdom, regulates the conduct of medical practice in the country. Its scope of action extends beyond the same, as it also defines and formulates criteria pertaining to performing research activity. Indeed, research governance (RG) is more like research regulation, and the DOH would largely assume the role of the regulation.

Study design is a fundamental aspect of research. If the design of a study is poor, no amount of clever analysis will provide reliable results. The results from poorly designed studies could be meaningless, and many resources will have been wasted, not to mention the possible risk to the subjects, which would be unethical. Therefore, it is essential that researchers invest adequate time and effort in designing their studies appropriately. It would be advisable to involve a medical statistician or an epidemiologist at the design stage of a study.

Immunohistochemistry describes the localization of antigens in histological and cytological preparations using antibodies. It is now recognized as an essential element and a major tool, both in diagnostic and research-orientated cellular pathology. The technique involves the detection of specific or highly selective cellular epitopes with an antibody and appropriate labelling system. Immunohistochemistry can be performed on cytological preparations, frozen sections and paraffin-embedded histological sections.

The fundamental aspect of cell culturing is to understand the type of cells that the investigator wishes to grow. There are many differences between the cell types; however, the easiest method of categorizing them is into primary cells and cell lines. Two types of cultured cell types:

The measurement of the physical and chemical characteristics of cells is called is the technique where these measurements are made individually of single particles (cells, nuclei, chromosomes), suspended within a stream of liquid, as they pass through a laser light source.

In the early 1970s, the possibility of mapping whole genomes arose, due to the prior discovery of bacterial enzymes that cut DNA at specific “restriction sites,” and the development of recombinant NA technologies and gene cloning. Nevertheless, one could not identify one single gene among thousands of fragments of DNA—until Edward Southern introduced his eponymous powerful DNA transfer and probing technique in 1975. He realized that restriction fragments can first be separated electrophoretically on an agarose gel and then be transferred to a nylon membrane by capillary action—the same way that blotting paper absorbs ink. Afterward, the blotted membrane can be incubated with a radioactive probe specific for the gene fragments of interest, which in turn become visible by placing an x-ray film on top of the membrane.

In situ hybridization (ISH) technique was introduced by Gall and Pardue in 1969. At that time the technique was limited by the use of radioactively labelled probes that were subsequently visualized by autoradiography. The development of interphase cytogenetics in the 1980s and fluorescent labels in 1986 has seen the technology applied in a number of fields. Although fluorescent in situ hybridization (FISH) is a valuable research tool, it is now also a technique employed in the diagnostic laboratory. It is currently a standard tool in cytogenetics laboratories, where it is used for the diagnosis of hereditary disorders, chromosomal aberrations, and hematologic cancer markers. More recently, the technique has been applied to formalin-fixed, paraffin-embedded cells and tissues. The application of FISH to detect gene amplifications (HER2 in breast cancer), gene rearrangements (BCR-ABL in leukaemias), microdeletions, chromosomal duplication, and viral infections (HPV) highlights the importance of this methodology, not only in the clinical setting but in wider research applications.

Since the first documentation of real-time polymerase chain reaction (PCR), it has been used for an increasing and diverse number of applications, including mRNA expression studies, DNA copy number measurements in genomic or viral DNAs, allelic discrimination assays, expression analysis of specific splice variants of genes and gene expression in paraffin-embedded tissues, and laser captured microdissected cells. Therefore, quantitative reverse transcriptase polymerase chain reaction (Q-RT-PCR) is now essential in molecular diagnostics to quantitatively assess the level of RNA or DNA in a given specimen. QRT-PCR enables the detection and quantification of very small amounts of DNA, cDNA, or RNA, even down to a single copy. It is based on the detection of fluorescence produced by reporter probes, which varies with reaction cycle number. Only during the exponential phase of the conventional PCR reaction is it possible to extrapolate back in order to determine the quantity of initial template sequence. The “real-time” nature of this technology pertains to the constant monitoring of fluorescence from specially designed reporter probes during each cycle. Due to inhibitors of the polymerase reaction found with the template, reagent limitation or accumulation of pyrophosphate molecules, the PCR reaction eventually ceases to generate template at an exponential rate (i.e., the plateau phase), making the end point quantitation of PCR products unreliable in all but the exponential phase.

The problems associated with expressing and purifying human proteins, especially in , the primary host organism for high-throughput (HTP) applications, are welldocumented and have plagued researchers for decades. Low yields due to toxicity, recombinant protein insolubility, and poor purification are just some of the problems that result in typical success rates from 2%–20% when expressing eukaryotic proteins in (Service). HTP structural genomic (SG) projects, such as NIH’s protein structure initiative (PSI) begun in 2000. Initially, the PSI focused on technology development to provide highly automated procedures for cloning, expression testing, protein purification, and protein crystallization, thus addressing production problems by increasing throughput. The development of these techniques has allowed PSI centers and other similar initiatives around the world to deposit over 2,000 novel protein structures in the Protein Dada Bank (PBD) as of January 2006 (PSI, http://www.nigms.nih.gov/Initiatives/PSI/). Nevertheless, despite the expenditure of significant resources, the rate of discovery is much less than hoped for at the beginning of the initiative due to bottlenecks at every stage of the pipeline as the problems mentioned above persist.

Although techniques such as RT-PCR and in situ hybridization (ISH) can give information about gene expression, they are limited in scope as typically one gene product is evaluated with each assay. The advent of transcriptional profiling using DNA microarray has revolutionized the field of molecular medicine as measurement of thousands of genes simultaneously in a given sample provide a vast amount of data for new disease classifications and biomarker discoveries. DNA microarray-based gene expression profiling relies on nucleic acid polymers, immobilized on a solid surface, which act as probes for complementary gene sequences. Microarrays typically contain several thousand single-stranded DNA sequences, which are “arrayed” at specific locations on a synthetic “chip” through covalent linkage. These DNA fragments provide a matrix of probes for fluorescently labeled complementary RNA (cRNA) derived from the sample of interest. The expression of each gene in the sample is quantified by the intensity of fluorescence emitted from a specific location on the array matrix which is proportional to the amount of that gene product ().