Breaking News
November 16, 2018 - Conditions that produce signs similar to arthritis
November 16, 2018 - AHA: Dapagliflozin Noninferior to Placebo for MACE in T2DM
November 16, 2018 - Surgery remains best treatment for appendicitis, Stanford study finds
November 16, 2018 - Researchers find no link between ‘allergy friendly’ dogs and lower risk of asthma
November 16, 2018 - Researchers elucidate new rules of connectivity of neurons in the neocortex
November 16, 2018 - Treating children with ‘bubble baby disease’
November 16, 2018 - Researchers find metabolite shuttle between cells in the liver that may combat tissue fibrosis
November 16, 2018 - AHA: PTSD Common Among Those Who Suffer Tear in the Aorta’s Wall
November 16, 2018 - Many RA patients’ pain related to central nervous system
November 16, 2018 - Changes in Himalayan gut microbiomes linked to diet
November 16, 2018 - Inhibition of prostaglandin E2 enhances ability to combat infectious colitis
November 16, 2018 - Chronic dry eye can slow reading rate and disrupt day to day tasks
November 16, 2018 - Researchers develop new drug molecule that inhibits inflammation
November 16, 2018 - Dementia symptoms peak in winter and spring, study finds
November 16, 2018 - Stanford tobacco researcher weighs in on JUUL
November 16, 2018 - Increasing omega-3 fatty acid intake during pregnancy reduces risk of premature birth, review finds
November 16, 2018 - Researchers find no link between infants waking up at night and later developmental problems
November 16, 2018 - Both parents and children agree about confidential medical services
November 16, 2018 - FDA warns against use of unapproved pain medications with implanted pumps
November 16, 2018 - Precision medicine-based approach to slow or reverse biologic drivers of Alzheimer’s disease
November 16, 2018 - Study provides new insight into norovirus outbreaks, may help guide efforts to develop vaccines
November 16, 2018 - Inexpensive, portable air purifier could help protect the heart from pollution
November 16, 2018 - New 15-minute scan could help diagnose brain damage in babies up to two years old
November 16, 2018 - Deep brain stimulation not effective for treating early Alzheimer’s
November 16, 2018 - Traditional chemotherapy superior to new alternative for oropharyngeal cancers | News Center
November 16, 2018 - What This Pond Protist Does With Its Genome Will Astound You
November 15, 2018 - Researchers develop tool that speeds up analysis and publication of biomedical data
November 15, 2018 - Scientists identify mechanism used by lung cancer cells to obtain glucose
November 15, 2018 - Abnormalities in development of the brain could be involved in onset of autism, finds new study
November 15, 2018 - Soy protein equally effective as animal protein in building muscle strength
November 15, 2018 - American Academy of Pediatrics, Nov. 2-6
November 15, 2018 - Dopamine drives early addiction to heroin
November 15, 2018 - Variance in gut microbiome in Himalayan populations linked to dietary lifestyle | News Center
November 15, 2018 - Reducing Cardiovascular Disease: The Amish Way
November 15, 2018 - King’s researchers launch charter to guide organizations to engage abuse survivors in research
November 15, 2018 - Enable Injections enters into development agreements with UCB and Apellis Pharmaceuticals
November 15, 2018 - TGen North collaborates with NARBHA Institute to advance human health
November 15, 2018 - Researchers discover molecular basis for therapeutic actions of an African folk medicine
November 15, 2018 - Human Cell Atlas study of early pregnancy shows how mother’s immune system is modified
November 15, 2018 - New guidelines for detecting and managing sarcopenia to be launched in the UK
November 15, 2018 - Researchers explore role of dietary composition on energy expenditure
November 15, 2018 - Elsevier launches Entellect™ Platform, unlocking value by creating AI-ready life sciences data
November 15, 2018 - Now that cannabis is legal in Canada, let’s use it to tackle the opioid crisis
November 15, 2018 - In the Spotlight: At the intersection of tech, health, and ethics
November 15, 2018 - Traditional Glaucoma Test Can Miss Severity of the Disease
November 15, 2018 - Researchers directly connect activities of genes with instinctive behavior in male cichlids
November 15, 2018 - Salk researchers report new methods to identify AD drug candidates with anti-aging properties
November 15, 2018 - St. Jude Hospital announces availability of largest collections of leukemia samples
November 15, 2018 - Attenua Announces First Patient Treated in Phase 2 Clinical Trial in Chronic Cough with Bradanicline
November 15, 2018 - Designing a novel cell-permeable peptide chimera to promote wound healing
November 15, 2018 - NEI investigators combine two imaging modalities to view the retina in unprecedented detail
November 15, 2018 - Determining how hearts develop to better understand congenital heart defects
November 15, 2018 - Maverick immune cells can act independently to identify and kill cancer cells, finds research
November 15, 2018 - Advanced AI and big data methods to tackle dementia
November 15, 2018 - Report reveals increase in pancreatic cancer death rates across Europe
November 15, 2018 - Luxia Scientific announces availability of its gut microbiome test in Luxembourg
November 15, 2018 - New diabetes drugs linked to increased risk of lower-limb amputation and ketoacidosis
November 15, 2018 - New approach targets matrix surrounding neurons to protect neurons after stroke
November 15, 2018 - Lilly Submits New Drug Application to the FDA for Lasmiditan for Acute Treatment of Migraine
November 15, 2018 - Heart failure patients shouldn’t stop meds even if condition improves: study
November 15, 2018 - Parents and carers of people with diabetes experience emotional or mental health problems
November 15, 2018 - RetiPharma secures funding to develop new peptide drug for treating degenerative eye disorders
November 15, 2018 - Breakthrough research could lead to a new wave of cancer-fighting antibodies
November 15, 2018 - Mylan and Biocon launch new insulin glargine biosimilar in the UK
November 15, 2018 - For wildfire safety, only particular masks guard against toxic particulate matter
November 15, 2018 - New study of tribe shows influence of Western diet and lifestyle on blood pressure
November 15, 2018 - Scientists harness power of natural killer cells to treat children with neuroblastoma
November 15, 2018 - Investigating foodborne disease outbreak in Bosnia and Herzegovina based on simulation game
November 15, 2018 - Recommendations Issued for Management of Bradycardia
November 15, 2018 - Benefit unclear due to a lack of suitable studies
November 15, 2018 - TAMEST recognizes UT Southwestern’s Ralph DeBerardinis for changing our understanding of cancer
November 15, 2018 - Researchers discover key factors behind intestinal inflammation in CVID patients
November 15, 2018 - CityU develops first microarrayed 3D neuronal culture platform
November 15, 2018 - Expert suggests ways to control uncomfortable vaginal symptoms in diabetic women
November 15, 2018 - New edition of Red Journal focuses on roles of imaging in radiation oncology
November 15, 2018 - Doctors Aren’t Promoting Breastfeeding’s Cancer-Protection Benefit
November 15, 2018 - Collection of demonstration projects highlights value of patient engagement in research
November 15, 2018 - Technique to ‘listen’ to a patient’s brain during tumour surgery
November 15, 2018 - Seven-year-old returns to life as a “normal, healthy child” following bone marrow transplant
November 15, 2018 - AMSBIO expands range of high quality FFPE cancer cell line controls
Gene sequencing reveals crucial molecular aspects of Trypanosoma brucei

Gene sequencing reveals crucial molecular aspects of Trypanosoma brucei

image_pdfDownload PDFimage_print

Trypanosoma brucei, which causes sleeping sickness, evades the immune system by repeatedly altering the structure of its surface coat. Sequencing of its genome and studies of its 3D genome architecture have now revealed crucial molecular aspects of this strategy.

Unicellular parasites belonging to the genus Trypanosoma cause sleeping sickness in humans. Sleeping sickness is a debilitating and potentially lethal disease in Sub-Saharan Africa, which is transmitted by the tsetse fly. Professor Nicolai Siegel, who heads a research group in molecular parasitology at LMU, uses trypanosomes as an experimental model system to study the incessant ‘arms race’ between parasites and their hosts: As the host immune system evolves ways of fighting parasitic infections, parasites continually develop strategies to outwit these mechanisms. Trypanosomes are specialists in the art of immune evasion. In a process known as antigenic variation, they constantly alter the structures of their surface coats, forcing the host’s immune system to redirect its fire against a novel target. Siegel’s group, in cooperation with colleagues based at the universities of Würzburg, ZB MED – Information Center for Life Sciences, TH Köln, the Helmholtz Institute for RNA-based Infection Research (HIRI) in Würzburg (an institute of the Helmholtz Zentrum for Infection Research) and institutions in the US, UK and Israel, have now taken a closer look at the genetic mechanisms that underlie the parasite’s ability to alter the proteins displayed on its surface. The researchers demonstrate that DNA packaging proteins which are involved in regulating access to specific segments of the parasite’s genome play a central role in the process. The new findings appear in the leading science journal Nature.

Trypanosomes infect a range of vertebrate organisms, and are usually transmitted to the final host by biting insects, which inject them into the mammalian bloodstream. The new study focuses on Trypanosoma brucei, which is not only responsible for sleeping sickness but also causes a condition known as nagana in cattle.

The T. brucei genome contains approximately 2000 genes that encode distinct variants of its surface coat protein. Crucially, only one of these is expressed on a given cell at any given time, and it covers the entire surface of the pathogen. Adaptive immune responses require the molecular recognition of invasive pathogens. Thus, the immune reaction initially mounted by the host during an infection is directed against the variant currently exposed on the surface of the trypanosome. However, by switching off the gene for the expressed surface protein and activating another instead, the parasite can effectively evade the host’s immune defense. Since it takes time for the immune system to recognize a new coat protein as ‘non-self’, the parasite is always one step ahead of the game, and can therefore establish a long-term infection.

“Our main interest is in how this genetic variability is regulated,” says Siegel, whose laboratory is part of the Faculty of Veterinary Medicine and currently located in LMU’s Biomedical Center. In the nucleus of the parasite, the chromosomal DNA molecules are wrapped around bead-like complexes made up of proteins called histones. In its condensed state – collectively referred to as heterochromatin – most of the DNA is inaccessible to enzymes and is therefore inactive. Accessibility to activation is largely controlled by attaching or removing small chemical tags to individual histone proteins or by replacing them with variant forms. To work out how the genes for surface proteins are selectively activated in trypanosomes, Siegel and colleagues first sequenced the entire genome of T. brucei and determined the three-dimensional configuration of the DNA within the nucleus. By analyzing the transcriptomes of single cells, they were able to show that switching from one form of the surface coat to another is stimulated by removal of two such histone variants. This results in a change in the three-dimensional structure of the DNA and an accompanying alteration of the overall packing density at these sites. These effects together make new gene sequences accessible to activation and enable new interactions between DNA segments to take place, which in turn allow other genes to be activated. “The important point is that both histone variants must be removed,” says Siegel. “When we removed only one of them, the three-dimensional structure of the DNA was altered, but there was no switch in the surface protein expressed.”

A better understanding of the mechanisms responsible for antigenic variation in trypanosomes promises to shed light on diseases other than sleeping sickness. Many other pathogens – including the causative organism of malaria, fungi of the genus Candida and many bacteria – use similar strategies to neutralize immune responses.

Source:

http://www.en.uni-muenchen.de/news/newsarchiv/2018/siegel_trypanosoma.html

Tagged with:

About author

Related Articles