For if you do not let My people go, I will let loose swarms of insects against you and your courtiers and your people and your houses; the houses of the Egyptians, and the very ground they stand on, shall be filled with swarms of insects. Exodus 8:17 (The Israel Bible™)
An international research group that includes Israeli scientists has deciphered genetic code – its sequence and genome structure – of the deadly parasite Trypanosoma brucei that causes sleeping sickness in sub-Saharan Africa. The discovery could lead to the development of treatments to protect people from it.
The parasite was discovered in 1894 by Sir David Bruce after whom the scientific name was given. T. brucei is transmitted between humans and other mammals with the help of the tsetse fly, allowing the parasite to multiply in its salivary glands and infect the mammals whose blood it sucks. It is one of only a few pathogens known to cross the blood brain barrier. There is an urgent need for the development of new drug therapies, as current treatments can have severe side effects and can prove fatal to the patient.
Initially, in the first stage of the disease, there are fevers, headaches, itchiness and joint pains. This begins one to three weeks after the bite. Weeks to months later, the second stage begins with confusion, poor coordination, numbness, and trouble sleeping. The disease is diagnosed by finding the parasite in a blood smear or in the fluid of a lymph node. Serious neurological symptoms and eventually death can occur unless medications are not given early.
About 70 million people living in 36 African countries are at risk for the disease from the parasite, which is commonly found in forests and bodies of water. An estimated 11,000 people are currently infected, and some 3,500 – most in the Democratic Republic of the Congo – die of it in an average year.
The prestigious journal Nature just reported a breakthrough in understanding the genome of the deadly parasite. The researchers analyzed both the genomic sequence and the three-dimensional structure of this parasite’s genome.
The international research was led by Prof. Nicolai Siegel of the University of Munich, who was assisted by researchers from Israel, Germany, the US and England. The genome sequence was analyzed using an innovative method developed by Dr. Noam Kaplan of the Rappaport Faculty of Medicine at the Technion-Israel Institute of Technology in Haifa.
The genome is the genetic information contained in the organism. The T. brucei genome has a very complex sequence that can contain billions of bases (DNA units). In the last two decades, there has been a quantum leap in human ability to decipher it. “Today, it is very easy to read millions of short segments of DNA, but you cannot read very long segments. Therefore, the main challenge is to correctly arrange the short sections, similar to assembling a puzzle – a process called the genome assembly,” Kaplan explained.
The Technion scientist also faced this challenge during his post-doctoral period at the University of Massachusetts. The technology is based on an experiment in which spatial proximity between DNA fragments in living cells is measured. In a paper published in the journal Nature Biotechnology five years ago, Kaplan showed how to assemble a human genome based on advanced computational analysis of spatial proximity patterns. “This method bridged ‘spatial gaps’ and is relevant to all living species in the world,” he said.
Since the development of the new method of assembling genomic sequences, several companies have been established on the basis of this principle and have recently been deciphered by many genomes of animals and plants. These include the frog, mosquito, goat, quinoa, wheat and barley. Now, as noted, it is the turn of the sleeping sickness parasite.
In this study, the researchers found a unique connection between the spatial organization of the genome and the mechanism for replacing the antigen – the protein that the human immune system identifies.
T. brucei can be used to escape the immune system of the affected person. The researchers believe that this discovery may in the future allow the development of treatments to protect the population prone to infection.
Kaplan joined the Rappaport Faculty of Medicine in 2016 and established an interdisciplinary laboratory. “To understand the genome, we need to integrate the fields of biology, computers, mathematics, statistics, physics and chemistry of the genome and how this organization affects the action of the genome. My research group is working on the next generation of genome-forming techniques that will enable us to characterize and understand the genetic changes occurring in cancer and other diseases,” Kaplan said.