Wednesday 11 June 2014

Malaria-carrying mosquitoes wiped out in lab with genetic method that creates male-only offspring

Mosquito sucking blood (stock image). In the first laboratory tests, a new method created a fully fertile mosquito strain that produced 95 per cent male offspring.Credit: © Henrik Larsson / Fotolia
Scientists have modified mosquitoes to produce sperm that will only create males, pioneering a fresh approach to eradicating malaria.

In a study published in the journal Nature Communications, scientists from Imperial College London have tested a new genetic method that distorts the sex ratio of Anopheles gambiae mosquitoes, the main transmitters of the malaria parasite, so that the female mosquitoes that bite and pass the disease to humans are no longer produced.

In the first laboratory tests, the method created a fully fertile mosquito strain that produced 95 per cent male offspring.

The scientists introduced the genetically modified mosquitoes to five caged wild-type mosquito populations. In four of the five cages, this eliminated the entire population within six generations, because of the lack of females. The hope is that if this could be replicated in the wild, this would ultimately cause the malaria-carrying mosquito population to crash.

This is the first time that scientists have been able to manipulate the sex ratios of mosquito populations. The researchers believe the work paves the way for a pioneering approach to controlling malaria.

Since 2000, increased prevention and control measures have reduced global malaria mortality rates by 42 per cent, but the disease remains a prevalent killer especially in vulnerable sub-Saharan African regions. Malaria control has also been threatened by the spread of insecticide resistant mosquitoes and malaria parasites resistant to drugs. According to latest estimates by the World Health Organization, over 3.4 billion people are at risk from contracting malaria and an estimated 627,000 people die each year from the disease.

Lead researcher Professor Andrea Crisanti from the Department of Life Sciences at Imperial College London said: "Malaria is debilitating and often fatal and we need to find new ways of tackling it. We think our innovative approach is a huge step forward. For the very first time, we have been able to inhibit the production of female offspring in the laboratory and this provides a new means to eliminate the disease."

Dr Nikolai Windbichler, also a lead researcher from the Department of Life Sciences at Imperial College London, said: "What is most promising about our results is that they are self-sustaining. Once modified mosquitoes are introduced, males will start to produce mainly sons, and their sons will do the same, so essentially the mosquitoes carry out the work for us."

In this new experiment the scientists inserted a DNA cutting enzyme called I-PpoI into Anopheles gambiae mosquitoes. In normal reproduction, half of the sperm bear the X chromosome and will produce female offspring, and the other half bear the Y chromosome and produce male offspring.
The enzyme that the researchers used works by cutting the DNA of the X chromosome during production of sperm, so that almost no functioning sperm carry the female X chromosome. As a result the offspring of the genetically modified mosquitoes was almost exclusively male.

It took the researchers six years to produce an effective variant of the enzyme.

"The research is still in its early days, but I am really hopeful that this new approach could ultimately lead to a cheap and effective way to eliminate malaria from entire regions. Our goal is to enable people to live freely without the threat of this deadly disease," concluded Dr Roberto Galizi from the Department of Life Sciences at Imperial College London.


Journal Reference:
  1. Roberto Galizi, Lindsey A. Doyle, Miriam Menichelli, Federica Bernardini, Anne Deredec, Austin Burt, Barry L. Stoddard, Nikolai Windbichler, Andrea Crisanti. A synthetic sex ratio distortion system for the control of the human malaria mosquito. Nature Communications, 2014; 5 DOI: 10.1038/ncomms4977

Saturday 7 June 2014

Schistosomiasis: Urinary Test Diagnoses Cancer and Infertility-Causing Parasite



Image: A Finnigan Surveyor Plus High-Performance Liquid Chromatography (HPLC) instrument (Photo courtesy of Thermo Scientific).
Image: A Finnigan Surveyor Plus High-Performance Liquid Chromatography (HPLC) instrument (Photo courtesy of Thermo Scientific).
Image: Ova of Schistosoma haematobium in a urinary bladder specimen (Photo courtesy of Michael E. DeBakey).
Image: Ova of Schistosoma haematobium in a urinary bladder specimen (Photo courtesy of Michael E. DeBakey).
A fast, noninvasive way to test for a cancer-causing parasite that kills hundreds of thousands of people every year has been discovered.

About 243 million people are infected with schistosomiasis, which kills about 200,000 people every year and following infection, women often contract female genital schistosomiasis, which affects the cervix and uterus resulting in bleeding and pain during sex and infertility.

Scientists at the University of Porto (Portugal) collaborating with their colleagues in Angola, conducted a cross-sectional study of female residents of a region in Bengo province (Angola), endemic for schistosomiasis haematobia. Ninety-three women and girls, aged from two to 94 years were interviewed on present and previous urinary, urogenital and gynecological symptoms and complaints. Urine was collected from the participants for egg-based parasitological assessment of schistosomal infection, and biochemical analysis.

The entire micturition volume was filtered through a polycarbonate membrane (Whatman plc; Springfield Mill, UK) and subsequently the membrane was stained with Trypan blue. Schistosome ova retained on the membrane were identified with the aid of a light microscope. Liquid chromatography diode array detection electron spray ionization mass spectrometry (LC/UV-DAD/ESI-MSn) was performed on a Finnigan Surveyor Plus High-Performance Liquid Chromatography (HPLC) instrument (ThermoFinnigan; San Jose, CA, USA) equipped with a diode-array detector and a mass detector.

The investigators discovered catechols in the urine of women who tested positively for parasite eggs, but not in the urine of uninfected women. The team also found an association between catechols and infertility. In studying the mechanisms involved, the team found that the catechols downregulate estrogen receptors and trigger DNA mutations. Either or both of these actions could be responsible for the bladder cancer and infertility common to schistosomiasis patients.

Monica Catarina Botelho, PhD, the senior author of the study said, “Estrogen metabolism/degradation is a normal body process as estrogens are degraded into catechols and these into quinones. But if there are too many quinones, due to an excessive estrogen production or altered metabolism, this can cause DNA damage, because they tend to bind to DNA disturbing it. Now we detect these molecules not only in the serum, but also in the urine of patients infected with Schistosoma, while uninfected patients do not have them. They have been linked before to cancer as in thyroid, breast and prostate neoplasms, and autoimmunity. Now we see them in infertility associated with schistosomiasis infection.” The study was published on May 21, 2014, in the journal Public Library of Science ONE.

source: www.labmedica.org