High throughput biology

High throughput biology (or high throughput cell biology) is the use of automation equipment with classical cell biology techniques to address biological questions that are otherwise unattainable using conventional methods. It may incorporate techniques from optics, chemistry, biology or image analysis to permit rapid, highly parallel research into how cells function, interact with each other and how pathogens exploit them in disease.[1]

High throughput cell biology has many definitions, but is most commonly defined by the search for active compounds in natural materials like in medicinal plants. This is also known as high throughput screening (HTS) and is how most drug discoveries are made today, many cancer drugs, antibiotics, or viral antagonists have been discovered using HTS.[2] The process of HTS also tests substances for potentially harmful chemicals that could be potential human health risks.[3] HTS generally involves hundreds of samples of cells with the model disease and hundreds of different compounds being tested from a specific source. Most often a computer is used to determine when a compound of interest has a desired or interesting effect on the cell samples.

Using this method has contributed to the discovery of the drug Sorafenib (Nexavar). Sorafenib is used as medication to treat multiple types of cancers, including renal cell carcinoma (RCC, cancer in the kidneys), hepatocellular carcinoma (liver cancer), and thyroid cancer. It helps stop cancer cells from reproducing by blocking the abnormal proteins present. In 1994, high throughput screening for this particular drug was completed. It was initially discovered by Bayer Pharmaceuticals in 2001. By using a RAF kinase biochemical assay, 200,000 compounds were screened from medicinal chemistry directed synthesis or combinatorial libraries to identify active molecules against activeRAF kinase. Following three trials of testing, it was found to have anti-angiogenic effects on the cancers, which stops the process of creating new blood vessels in the body.[4][5]

Another discovery made using HTS is Maraviroc. It is an HIV entry inhibitor, and slows the process and prevents HIV from being able to enter human cells.[6] It is used to treat a variety of cancers as well, reducing or blocking the metastasis of cancer cells, which is when cancer cells spread to a completely different part of the body from where it started. High throughput screening for Maraviroc was completed in 1997, and finalized in 2005 by Pfizer global research and development team.

High-throughput biology serves as one facet of what has also been called "omics research" - the interface between large scale biology (genome, proteome, transcriptome), technology and researchers. High throughput cell biology has a definite focus on the cell, and methods accessing the cell such as imaging, gene expression microarrays, or genome wide screening. The basic idea is to take methods normally performed on their own and do a very large number of them without impacting their quality [7]

High throughput research can be defined as the automation of experiments such that large scale repetition becomes feasible. This is important because many of the questions faced by life science researchers now involve large numbers. For example, the Human Genome contains at least 21,000 genes,[8] all of which can potentially contribute to cell function, or disease. To be able to capture an idea of how these genes interact with one another, which genes are involved in and where they are, methods that encompass from the cell to the genome are of interest.

  1. ^ Hsiao, A., & Kuo, M. D. (2009). High-throughput Biology in the Postgenomic Era. Journal of Vascular and Interventional Radiology, 20(7), S488–S496. https://doi.org/10.1016/j.jvir.2009.04.040
  2. ^ Kalinina MA, Skvortsov DA, Rubtsova MP, Komarova ES, Dontsova OA. Cytotoxicity Test Based on Human Cells Labeled with Fluorescent Proteins: Fluorimetry, Photography, and Scanning for High-Throughput Assay. Molecular Imaging & Biology. 2018;20(3):368-377. doi:10.1007/s11307-017-1152-0
  3. ^ Mezencev, Roman; Subramaniam, Ravi (October 2019). "The use of evidence from high-throughput screening and transcriptomic data in human health risk assessments". Toxicology and Applied Pharmacology. 380: 114706. doi:10.1016/j.taap.2019.114706. PMC 9624462. PMID 31400414.
  4. ^ Hautier G. Finding the needle in the haystack: Materials discovery and design through computational ab initio high-throughput screening. Computational Materials Science. 2019;163:108-116. doi:10.1016/j.commatsci.2019.02.040
  5. ^ Yao, Yao; Wang, Tianqi; Liu, Yongjun; Zhang, Na (4 December 2019). "Co-delivery of sorafenib and VEGF-siRNA via pH-sensitive liposomes for the synergistic treatment of hepatocellular carcinoma". Artificial Cells, Nanomedicine, and Biotechnology. 47 (1): 1374–1383. doi:10.1080/21691401.2019.1596943. PMID 30977418.
  6. ^ Maraviroc. AHFS Consumer Medication Information. September 2019:1.
  7. ^ Taly, Valerie, Bernard T. Kelly, and Andrew D. Griffiths. "Droplets as microreactors for high‐throughput biology." ChemBioChem 8.3 (2007): 263-272.
  8. ^ "How Many Genes Are There?". Human Genome Project Information. U.S. Department of Energy Office of Science. 2008-09-19.

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