In recent years a number of epidemics have caused major health concerns and economic repercussions. These include epidemics caused by coronaviruses such as Severe Acute Respiratory Syndrome CoronaVirus (SARS-CoV), Middle East Respiratory Syndrome CoronaVirus (MERS-CoV) and SARS-CoV-2, which is the cause of the current COVID-19 pandemic. The tools and medications that can be used against such pathogens, which cause disease or illness to its host, are limited, especially considering the rapid way in which they mutate and spread.
A team of researchers from the Department of Applied Biomedical Science at the University of Malta’s Faculty of Health Sciences, the Faculty of Medicine and Surgery and the Centre for Molecular Medicine and Biobanking is conducting a project called TargetID – Novel Drug Targets for Infectious Diseases – to identify new treatments to prevent the severe outcomes of infectious diseases, starting with SARS-CoV-2.
SARS-CoV-2 and many other viruses kill or cause severe effects due to cytokine storms, where the body produces excessive inflammatory molecules in an attempt to get rid of the pathogen, resulting in damaging effects on the host’s own cells and organs. The team of researchers in TargetID will identify genes that regulate the levels of molecules that are deranged after infection with SARS-CoV-2.
The whole genome (the DNA) of around 1,000 Maltese individuals, together with their RNA sequence, will be sequenced. RNA is produced from DNA generally as an intermediate for the production of protein. A combination of approaches, including focusing on data from families and on biological pathways, will be adopted. Biological pathways are groups of molecules that interact together to perform some function, such as signalling the presence of a pathogen and initiating an immune response.
These approaches will be used to analyse this high throughput sequencing data in search of relevant genes and genetic variants that can serve as novel drug targets. Genetic variants that alter risk for severity of COVID-19 infection will also be identified.
The extensive data obtained will be useful beyond the end of this project as it can be used for any other pathogen that influences gene expression in blood; it will also be useful for other conditions such as diabetes and myocardial infarction.
This project (COV.RD.2020-11), led by Dr Stephanie Bezzina Wettinger, is funded through the MCST COVID-19 R&D Fund 2020, which is jointly administered by the Malta Council for Science and Technology and Malta Enterprise.
More details about the research team and the project can be found on the project website www.um.edu.mt/projects/targetid.
Stephanie Bezzina Wettinger, Rosienne Farrugia, David Saliba are senior lecturers
Did you know?
• If stretched out, the human genome would extend to about two metres. Almost all human cell types have two copies of the human genome. Gametes (sex cells) have only one copy and red blood cells do not have any copies at all.
• The human genome is currently estimated to have around 21,000 protein coding genes. Each of these can make more than one protein.
• An almost equal number of genes that do not code for protein but produce RNA have also been identified.
• There are six million differences in the DNA sequence of any two unrelated individuals.
For more trivia see: www.um.edu.mt/think
Sound bites
• The Human Genome project provided the first entire sequence of human DNA, which is a code consisting of 3.2 billion base pairs (represented with the letters A, C, G, T). It took a large international consortium 15 years to complete. The first working draft of the human genome sequence cost an estimated €245 million ($300 million), and required a further €125 million ($150 million) to obtain the finished sequence. Today it is possible to sequence several whole human genomes in less than a week at a cost that is below €1,000 per sample.
https://www.genome.gov/about-genomics/fact-sheets/Sequencing-Human-Genome-cost
• Sequencing a human genome generates around 200 gigabytes of raw data. Using the latest technology, the DNA is broken up into small fragments, sequenced and then the position of each fragment is found on the reference genome sequence. The sequence is then compared and differences, some of which may be disease causing, are identified for further studies.
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