#kinetoplastids

[wikipediapictures]

African trypanosomiasis

“Trypanosoma forms in blood smear from patient with African trypanosomiasis.” - via Wikimedia Commons

[evoldir]

Fwd: Postdoc: DalhousieU.Two.ComparativeGenomics

Begin forwarded message: > From: evoldir@evol.biology.mcmaster.ca > Subject: Postdoc: DalhousieU.Two.ComparativeGenomics > Date: 26 September 2023 at 09:16:41 BST > To: rdmpage@gmail.com > > > > TWO POSTDOCTORAL POSITIONS > > Endosymbiosis,comparative genomics, gene transfer,functional proteomics, > mass spectrometry, bioinformatics > > Archibald and Hesketh Labs > > Department of Biochemistry and Molecular Biology, Dalhousie University > > Halifax, Nova Scotia CANADA > > We are looking for two skilled, motivated and curious postdoctoral > researchers to investigate molecular and cellular aspects of endosymbiosis > in members of the genus Paramoeba, enigmatic Amoebozoa that harbour > obligate eukaryotic endosymbionts of kinetoplastid ancestry.The > successful applicants will work to develop and apply molecular, genetic > and biochemical approaches to the study of host-endosymbiont interactions > in Paramoeba species.Ideal candidates will have experience in some > combination of microbiology, genetics, proteomics or bioinformatics, > evidenced by peer reviewed publications in internationally recognized > journals.Strong written and oral communication abilities are essential. > > In connection with Dalhousie's Institute for Comparative Genomics, > the Archibald and Hesketh labs are part of a collegial and internationally > recognized community of comparative genomics and molecular evolution > researchers.  The successful applicants will have the opportunity to > work collaboratively with these researchers and with those at other > institutions. > > The positions are available starting immediately and will run for > an initial 1-year period, with the possibility of extension up to 3 > years given satisfactory performance. Salary is set at $70,000 (CAD) > per year. All qualified and interested persons are encouraged to apply, > with applications from members of under-represented communities and > equity-seeking groups particularly encouraged. Applicants should email (1) > a brief cover letter outlining their research interests and qualifications > as they relate to these positions, (2) a Curriculum Vitae and (3) contact > information for three references to John Archibald at jmarchib@dal.ca. > > > > John Archibald

[rnomics]

Hammerhead #ribozyme-based U-insertion and deletion #RNA editing assays for multiplexing in HTS applications [Method]

Untranslatable mitochondrial transcripts in kinetoplastids are decrypted post-transcriptionally through an RNA editing process that entails uridine insertion/deletion. This unique stepwise process is mediated by the editosome, a multiprotein complex that is a validated drug target of considerable interest in addressing the unmet medical needs for kinetoplastid diseases. With that objective, several in vitro RNA editing assays have been developed, albeit with limited success in discovering potent inhibitors. This manuscript describes the development of three hammerhead #ribozyme (HHR) FRET reporter-based RNA editing assays for pre-cleaved deletion, insertion, and ligation assays that bypass the rate-limiting endonucleolytic cleavage step, providing information on U-deletion, U-insertion, and ligation activities. These assays exhibit higher editing efficiencies in shorter incubation times while requiring significantly less purified editosome and 10,000-fold less ATP than the previously published full round of in vitro RNA editing assay. Moreover, modifications in the reporter #ribozyme sequence enable the feasibility of multiplexing a #ribozyme-based insertion/deletion editing (RIDE) assay that simultaneously surveils U-insertion and deletion editing suitable for HTS. These assays can be used to find novel chemical compounds with chemotherapeutic applications or as probes for studying the editosome machinery. http://rnajournal.cshlp.org/cgi/content/short/rna.079454.122v1?rss=1&utm_source=dlvr.it&utm_medium=tumblr

[most-definitely-human]

This is my first experience with this type of immunofluorescence and I’m really happy with how it came out! These are procyclic forms of T. brucei, a parasitic kinetoplastid that causes sleeping sickness. The procyclin glycoprotein covering the surface of the cells is immunolabelled in green and the DNA is fluorescing in blue due to DAPI, a fluorescent stain that binds strongly to adenine–thymine-rich regions in the nucleus and kinetoplast of each parasite.

[secrettreestuffidk]

Consider the kinetoplastid:

basically all “worm on a string” comparisons to actual animals pale in comparison to the fucking pipehorse

[dhominis]

okay, yeah, I just don’t like flatworms

This isn’t a “parasites are gross” post, I love apicomplexans (!!) and parasitic nematodes and kinetoplastids and weird bacterial/viral pathogens, love cool metazoan ectoparasites, love Dermatobia hominis.

But flatworms are just... look, okay, usually I learn about a cool parasite and it’s just got all these briliant adaptations. Bot larvae secrete bacteriostatic compounds! Interactions between Plasmodium and host RBC receptors! How really high host mortality can actually be adaptive for parasites that are transmitted by e.g. bedbugs/fleas!  Everything about Trypanosoma cruzi genetics and physiology and pathogenesis! Most parasites are just beautiful and elegant

The platyhelminths, on the other hand, are like okay, oh sure, you burrowed up the bile duct, congratulations. Oh, what’s that, you’re just gonna build inflammatory nodules in the lung? You’re dropping proglottids off into the intestinal lumen? You’re hanging out in essentially randomly chosen parts of the intermediate host’s body because it doesn’t matter to you? Great. Keep doing that, I guess. Utterly artless, but you do you. Live your best life.

Dick.

(schistosomes are kind of neat, I’ll give ‘em that)

[bpod-bpod]

Screening for Solutions

Developing better means of screening for and identifying useful drugs is a key step towards more effective and accessible treatments for patients, especially in poorer parts of the world. Visceral leishmaniasis, caused by infection with Leishmania parasites, is one potentially deadly disease for which more easily distributable treatments are badly needed. Drugs currently available are either very expensive or require a long period of hospitalisation, and can have serious side effects. To identify more suitable medicines, researchers tested the effect of over 170 compounds on macrophages, cells of the immune system, infected with Leishmania parasites (pictured with cell nuclei in red and parasites in green). They monitored the impact of each potential drug on disease progression over several days to measure their speed of action, a key parameter in determining the most effective compounds. Further work on the drugs identified in this assay could yield new treatments in the future.

Written by Emmanuelle Briolat

Image by Imanol Peña-Urquiza

Kinetoplastids DPU, Diseases of the Developing World, GlaxoSmithKline, Tres Cantos, Madrid, Spain

Image originally published under a Creative Commons Licence (BY 4.0)

Research published in PLOS Neglected Tropical Diseases, May 2017

We want to improve BPoD. Please take a minute to answer our simple survey. It will make a huge difference!

You can also follow BPoD on Instagram, Twitter and Facebook

[clevelandstate]

Dr. Amit Gaurav Works to Combat Sleeping Sickness

Dr. Amit Gaurav explored many American universities, but Cleveland State University stood out to him.

Originally from India, Gaurav was attracted to CSU because of the work being done in its Center for Gene Regulation in Health and Disease (GRHD). One of the labs in the center, run by Dr. Bibo Li, has been focused on telomeres and protozoan parasites, which was perfect for Gaurav, who specializes in molecular parasitology.

Gaurav attended Banaras Hindu University for his undergraduate degree and obtained his masters and Ph.D. from Jawaharlal Nehru University in New Delhi, India. He began his work as a post-doctoral fellow at CSU in the fall of 2016.

While it may not be as big as the universities Gaurav was used to seeing in India, Gaurav is enjoying his time at Cleveland State.

“It’s very interesting,” Gaurav says. “It’s very vibrant.”

As a post-doctoral fellow, Gaurav focuses on his research and doesn’t technically teach in a classroom setting. However, he does mentor and support undergraduates and Ph.D. candidates, providing directions on lab work, procedures and experiments.

During his time at CSU, Gaurav has been conducting research on Trypanosoma brucei (T. brucei), a protozoan parasite that causes African trypanosomiasis, commonly known as African sleeping sickness. The disease is usually transferred via a bite by an infected tsetse fly and can be fatal if untreated.

While treatment for sleeping sickness exists, “current anti-trypanosome drugs are highly toxic, which greatly limits their efficacy.”

Specifically, Gaurav is interested in studying T. brucei telomeres. Telomeres are nucleoprotein complexes that protect the end of chromosomes. Telomeres help maintain genome integrity and stability.

“We like to say it is like the end of a shoelace where the plastic piece is,” Gaurav said regarding telomeres. “It protects the shoelace from fraying.”

The T. brucei parasite regularly changes its surface coat by switching its major surface antigen in order to evade the host’s immune response. Because the major surface antigen is expressed from telomere-adjacent regions, Dr. Li’s team has been focusing on telomere functions in antigenic variation. The Li lab has found that T. brucei telomere proteins regulate this switching in more than one way and are critical for survival of the parasite.

“It’s really hard to kill a parasite, especially if it is in a host,” Gaurav says. “This particular parasite is very interesting because it can change its coat.” 

Eventually the parasite can cross the blood-brain barrier and cause severe neurological defects.

The more the lab discovers about roles of telomere proteins in pathogenesis, the better chance there is to find a more effective cure.

Gaurav recently presented a talk about his research at the prestigious Kinetoplastid Molecular Cell Biology Meeting at the Marine Biological Laboratory in Woods Hole, Massachusetts. During this meeting, scientists and researchers gather to present and critique research that is currently a work-in-progress.

“Because you are presenting your ongoing research, you get a lot of feedback,” Gaurav says. “It’s very invaluable but it’s also very competitive”.

“It lets you improve your work,” Gaurav continues. “After we come back from meetings like that, we optimize our approaches and expedite our work and then we publish it.”

Gaurav presented a talk about the telomere protein RAP1, which the GRHD lab has already done much work on. According to Gaurav, they have found a new mode of function for the protein.

“It was a very nice experience,” Gaurav says. “I discussed questions with experts in the field from around the world, so it was very helpful for my research.”

Gaurav and the team in the lab will continue to work on their T. brucei research and hope to soon publish their findings on the RAP1 protein.

[evoldir]

Fwd: Graduate position: Durham.Endosymbiosis

Begin forwarded message: > From: evoldir@evol.biology.mcmaster.ca > Subject: Graduate position: Durham.Endosymbiosis > Date: 30 October 2020 at 06:11:03 GMT > To: rdmpage@gmail.com > > > > > PhD Opportunity: > > Summary: Endosymbiosis is recognised as a fundamental evolutionary > innovation that underpins the origins of many unicellular and all > multicellular lifeforms (Chomicki et al., 2019). Understanding the > biology of such phenomena can shed light on key drivers of inter-species > cooperation and provide an important window into early origins of cellular > life on the planet. The PhD student will link to a recently funded > project to deploy new tools: single cell genomics and transcriptomics, > as well as metabolomics; to explore a unique and poorly understood > endosymbiosis involving an emergent disease agent of major economic > importance. Supported by a world class supervisory team (Prof. Mike > Barrett, Dr. Martin Llewellyn, Wellcome Trust Centre for Integrative > Parasitology, Glasgow; Dr. Guillame Chimocki, Life Sciences, Durham) and > a range in international collaborators (Prof. John Archibald, Dalhousie > University, Canada; Dr. Neil Ruane, Marine Institute, Ireland), the > student will have the opportunity to develop skills at the cutting edge > of genomics and molecular biology, undertake training at international > centres of excellence in parasitology and evolutionary biology in the UK > and North America, and engage in marine biological fieldwork on the west > coast of Ireland and Scotland.  Finally, this project has strong links > with aquaculture industry via project partners Scottish Sea Farms (SSF, > Dr. Ralph Bickerdike) and the student will also get valuable experience > working alongside industry. > > Secondary endosymbiosis: The phenomenon in which eukaryotic organisms > engulf other eukaryotes is termed ‘secondary endosymbiosis’. Secondary > endosymbiosis underpins the evolution of many eukaryotic phototrophs > and is thought to have involved the engulfment of an ancestral > eukaryotic rhodophyte (Oborník 2018). The number of times this has > occurred in evolutionary history is a moot point. However, it is > clear that rhodophyte-origin plastids play a key role in their host > cell’s biology. In some cases, the symbiont has lost the ability to > photosynthesize, which leaves them a relic non-photosynthetic plastid in > a secondarily heterotrophic cell. This is the case for the apicomplexans, > which include the causative agents of toxoplasmosis and malaria. The > basis of ongoing metabolic dependency is not always clear, however some > conserved functions across plastids belonging to different apicomplexan > lineages include isoprenoid (IPP and DMAPP), tetrapyrrole, and fatty > acid biosynthesis (Janouškovec et al. 2015). > > The study system: Paramoeba perurans causes amoebic gill disease (AGD) > and is a major pathogen in salmonid aquaculture, causing  £400 million > in losses per annum world-wide. There are currently no drugs available to > treat AGD. P. perurans has a unique cellular biology that can be readily > exploited given the right tools. Enclosed within its cytoplasm is a > bizarre endosymbiont – Perkinsela. Genomic sequence data suggest that > the basic physiology of this endosymbiont has many of the same biochemical > features as found in kinetoplastid pathogens of man and domestic livestock > (e.g. Sleeping sickness, Leishmaniasis and Chagas disease). > > The endosymbiosis between P. perurans and Perkinsela is unique among > eukaryotes because it does not involve an originally photosynthetic > symbiont. Prior investigations have established interdependence between > the kinetoplasitid and amoeba based on predicted gene content and ontogeny > in the related Parameoba pemaquidensis (Tanifuji et al. 2017). > > This studentship has three major aims: > > Aim 1: Understand the molecular basis of the obligate dependence between > P. perurans and Perkinsela. The student will use genome sequencing (long > read technologies jointly with illumina short reads for polishing), > single-cell transcriptomics as well as metabolomics to dissect the > molecular basis of the symbiosis. Specific drug knock outs jointly > with transcriptomic analysis will allow to functionally test metabolic > dependences. > > Aim 2: Undertake rational Amoebic gill disease (AGD) drug discovery. A > detailed understanding of dependences in the between P. perurans and > Perkinsela symbiosis will provide a window to test drugs efficient on > AGD. In collaboration with the Wellcome Trust Centre for Intergrative > Parasitology, the student will test drugs targeting metabolic dependences > of P. perurans. Ultimately trials will be performed in fish farms > with SSF. > > Aim 3: Trace the evolution of this unique endosymbiosis. Using a recent > approach (Kwong et al., 2019), we will reconstruct the phylogenetic > histories of both the host P. perurans and the Perkinsela symbiont clades, > relying on a range of archival environmental samples as well as new marine > collections. Using targeted sequence enrichment, we will sequence the > genomic regions of the host identified as driving the obligate dependence > (Aim 1), and analyses of substitution rates (dn/ds) will inform of their > functionality. When possible, close relatives will be cultured to assay > the presence of the symbiont using microscopy and FISH. This will allow > t evolutionary history of this unique endosymbiosis, specifically testing > (i) the number of origins of this symbiosis across the clade encompassing > P. perurans, (ii) whether the obligate dependence has been lost or is > retained throughout the clade, and (iii) whether all P. perurans strains > evolved the same or distinct dependences on Perkinsela. > > Methodology > Via genome sequencing, standard and single-cell transcriptomics, as well > as metabolomic analyses to validate predicted pathways, the student will > establish the role of Perkinsela in P. perurans biology. At the University > of Glasgow, the student will undergo training in genome sequencing and > annotation (Aim 1 and 2). At Durham University, Biosciences, the student > will receive training in key ecological and evolutionary theory around > symbioses as well as in-depth phylogenetic comparative methods including > phylogenetic inference, ancestral state estimation and gene substitution > rate with the aim of reconstructing the origins of the symbiosis (Aim > 3). At the University of Glasgow, Wellcome Trust Centre for Integrative > Parasitology the student will learn how to exploit plastid-targeted drug > knock-outs and single cell sequencing to unpick the metabolic interactions > between host and symbiont. During a secondment to John Archibald’s > laboratory at Dalhousie University, Canada, the student will receive > further training in amoebozoan genome assembly and annotation with > particular reference to secondary endosymbiosis. > > Project Timeline > Year 1 > Student, assisted by PIs and dedicated post-docs, sequences P. perurans > genome and transcriptome. Visits Canada to undertake training in genome > assembly > > Year 2 > Student assists with targeted drug knock-outs of P. perurans > organelles alongside metabolomics and transcriptomics to unpick > ecological/biochemical basis of symbiosis > > Year 3 > Student will undertake sample collection and sequencing of P. perurans > and symbiont clades to establish the evolution of the symbiosis > > Year 3.5 > Data analysis > > Training & Skills > The student will receive training in genomics, transcriptomics > (inc. single cell), phylogenetic, metabolomics, molecular biology, > microscopy and more. The student will have access to world class > supervision and benefit from links to international research networks > as well as to industry. > > References & further reading > Rodger HD (2013.) Amoebic gill disease (AGD) in farmed salmon (Salmo > salar) in Europe. . Fish Veterinary Journal 16. > > Harmer J, Yurchenko V, Nenarokova A, Lukeš J, and Ginger ML 2018 Farming, > slaving and enslavement: histories of endosymbioses during kinetoplastid > evolution Parasitolgy 145, pp. 1311-1323 > > Creek DJ, Barrett MP (2013) Determination of antiprotozoal drug mechanisms > by metabolomics approaches. Parasitology 141: 83-92. > > Schwabl, P., Imamura, H., Van den Broeck, F. … & Llewellyn, MS Meiotic > sex in Chagas disease parasite Trypanosoma cruzi. Nat Commun 10, 3972 > (2019) > > Räz B, Iten M, Grether-Bühler Y, Kaminsky R, Brun R (1997) The Alamar > Blue® assay to determine drug sensitivity of African trypanosomes > (T.b. rhodesiense and T.b. gambiense) in vitro. Acta Tropica 68: 139-147. > > Chomicki, G., Weber, M., Antonelli, A., Bascompte, J. and Kiers, E.T., > 2019. The impact of mutualisms on species richness. Trends in ecology & > evolution, 34(8), pp.698-711. > > Chomicki, G., Kiers, E.T. and Renner, S.S., 2020. The evolution of > mutualistic dependence. Annual Review of Ecology, Evolution, and > Systematics, 51. (in press) > > Kwong, W.K., Del Campo, J., Mathur, V., Vermeij, M.J. and Keeling, > P.J., 2019. A widespread coral-infecting apicomplexan with chlorophyll > biosynthesis genes. Nature, 568(7750), pp.103-107. > > HOW TO APPLY > > Application procedure: For applications to the University > of Glasgow please use the dedicated application portal: > https://ift.tt/37ZUUi5 (you will still need to submit > your administrative details to the IAPETUS2 website as well > -https://ift.tt/3kJvkRL > > All enquiries please > email martin.llewellyn@glasgow.ac.uk > > Martin Llewellyn > via IFTTT

[rnomics]

KRGG1 function in #RNA editing in Trypanosoma brucei [Article]

Mitochondrial gene expression in trypanosomes requires numerous multiprotein complexes that are unique to kinetoplastids. Among these, the most well characterized are RNA Editing Catalytic Complexes (RECCs) that catalyze the guide RNA (gRNA)-specified insertion and deletion of uridines during mitochondrial mRNA maturation. This post-transcriptional resequencing of mitochondrial mRNAs can be extensive, involving dozens of different gRNAs and hundreds of editing sites with most of the mature mRNA sequences resulting from the editing process. Proper coordination of the editing with the cognate gRNAs is attributed to RNA Editing Substrate-binding Complexes (RESCs), which are also required for RNA editing. Although the precise mechanism of RESC function is less well understood, their affinity for binding both editing substrates and products suggests that these complexes may provide a scaffold for RECC catalytic processing. KRGG1 has been shown to bind RNAs, and although affinity purification co-isolates RESC complexes, its role in RNA editing remains uncertain. We show here that KRGG1 is essential in BF parasites and required for normal editing. KRGG1 repression results in reduced amounts of edited A6 mRNA and increased amounts of edited ND8 mRNA. Sequence and structure analysis of KRGG1 identified a region of homology with RESC6, and both proteins have predicted tandem helical repeats that resemble ARM/HEAT motifs. The ARM/HEAT-like region is critical for function as exclusive expression of mutated KRGG1 results in growth inhibition and disruption of KRGG1 association with RESCs. These results indicate that KRGG1 is critical for RNA editing and its specific function is associated with RESC activity. http://rnajournal.cshlp.org/cgi/content/short/rna.079418.122v1?rss=1&utm_source=dlvr.it&utm_medium=tumblr

[csrgood]

Novartis and DNDi to Collaborate on the Development of a New Oral Drug to Treat Visceral Leishmaniasis

Novartis and the Drugs for Neglected Diseases initiative (DNDi), a not-for-profit research and development (R&D) organization, have signed a collaboration and licence agreement to jointly develop LXE408, as a potential new oral treatment for visceral leishmaniasis, one of the world’s leading parasitic killers.

LXE408 is a first-in-class compound, discovered at Novartis with financial support from the Wellcome Trust.  Within the scope of the agreement, Novartis is responsible for completing Phase I clinical trials. In addition, it will drive pharmaceutical development and regulatory submissions. Upon approval, Novartis has committed to distributing the drug on an affordable basis worldwide with a focus on maximizing access in endemic countries.

DNDi will lead Phase II and Phase III clinical development, with the first Phase II study scheduled to start in early 2021 in India. Additional trials are planned to take place in East Africa, which has the highest burden of visceral leishmaniasis.

“Existing treatments for visceral leishmaniasis are simply not good enough. They are too long, increasingly ineffective, and can be toxic, painful, and costly,” said Dr Bernard Pécoul, Executive Director of DNDi. “Our hope is to radically transform this by developing new oral drugs that are affordable, safe, effective, easy to take, and can also be adapted to meet the treatment needs of patients in different countries.”

Over one billion people worldwide are at risk of leishmaniasis, which is transmitted by the bite of a sand fly. Visceral leishmaniasis, also known as kala-azar, is the most serious form of leishmaniasis, causing fever, weight loss, spleen and liver enlargement, and if left untreated, death. There are an estimated 50 000 to 90 000 new cases per year. Treating the disease is complex as it is dependent on the species of infecting parasite and the country, as treatment responses differ from region to region.

“Novartis has a long-term commitment to neglected tropical diseases that spans several decades. Diseases caused by kinetoplastid parasites, such as leishmaniasis, are one of our strategic research priorities and, together with our partners, we have developed a promising portfolio of drug candidates,” said Dr Lutz Hegemann, Chief Operating Officer for Global Health at Novartis. “We are excited to collaborate with DNDi to reimagine treatment options for people with leishmaniasis around the world.”

Broader partnerships

The collaboration between DNDi and Novartis is aligned with a broader program with the Wellcome Trust and other partners to develop new combinations of entirely new, all-orally acting chemical entities, to treat visceral leishmaniasis and cutaneous leishmaniasis, another form of the disease.

The program brings together a strong consortium of R&D partners, including the University of Dundee, GSK, Pfizer, TB Alliance, and Takeda Pharmaceutical Company Limited. These partners have built a portfolio of lead series, pre-clinical and clinical drug candidates, originating from different chemical classes with different mechanisms of action against leishmania parasites. 

“We are delighted to be partnering with Novartis from drug development to delivering a promising new oral treatment for visceral leishmaniasis. Together, we can contribute to sustaining elimination efforts in India and altering the treatment landscape in East Africa,” said Dr Fabiana Alves, Head of Visceral Leishmaniasis Clinical Program at DNDi.

Disclaimer

This media update contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as “potential,” “can,” “will,” “plan,” “expect,” “anticipate,” “look forward,” “believe,” “committed,” “investigational,” “pipeline,” “launch,” or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for the investigational or approved products described in this media update, or regarding potential future revenues from such products or regarding the collaboration described in this media update. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that the investigational or approved products described in this media update will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Neither can there be any guarantee that the collaboration described in this media update will achieve any of its intended goals and objectives in the expected time frame, or at all. Nor can there be any guarantee that such products will be successful in the future. In particular, our expectations regarding such products and the collaboration described in this media update could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures and requirements for increased pricing transparency; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; general political and economic conditions; safety, quality, data integrity, or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, and other risks and factors referred to in Novartis AG’s current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this media update as of this date and does not undertake any obligation to update any forward-looking statements contained in this media update as a result of new information, future events or otherwise.

About Novartis

Novartis is reimagining medicine to improve and extend people’s lives. As a leading global medicines company, we use innovative science and digital technologies to create transformative treatments in areas of great medical need. In our quest to find new medicines, we consistently rank among the world’s top companies investing in research and development. Novartis products reach more than 750 million people globally and we are finding innovative ways to expand access to our latest treatments. About 109,000 people of more than 145 nationalities work at Novartis around the world. Find out more at www.novartis.com

Novartis is on Twitter. Sign up to follow @Novartis at https://twitter.com/novartisnews

For Novartis multimedia content, please visit https://www.novartis.com/news/media-library

For questions about the site or required registration, please contact media.relations@novartis.com

About DNDi

A not-for-profit research and development organization, DNDi works to develop new treatments for people living with neglected diseases, notably Chagas disease, sleeping sickness (human African trypanosomiasis), leishmaniasis, filarial infections, mycetoma, pediatric HIV, and hepatitis C. Since its inception in 2003, DNDi has delivered eight new treatments, including new drug combinations for kala-azar, two fixed-dose antimalarials, and DNDi’s first successfully developed new chemical entity, fexinidazole, approved in 2018 for the treatment of both stages of sleeping sickness.

# # #

Novartis Media Relations

E-mail: media.relations@novartis.com

  Antonio Ligi

  Novartis External Communications

  +41 61 324 1374Call: +41 61 324 1374 (direct)

  antonio.ligi@novartis.com

    Eric Althoff

  Novartis US External Communications

  +1 646 438 4335Call: +1 646 438 4335

  eric.althoff@novartis.com

Katerina Kontzalis

  Global Health & CR Communications

  +41 61 324 1631Call: +41 61 324 1631 (direct)

  +41 79 797 8393Call: +41 79 797 8393 (mobile)

  katerina.kontzalis@novartis.com

  Novartis Investor Relations

Central investor relations line: +41 61 324 7944

E-mail: investor.relations@novartis.com

  Central   North America   Samir Shah +41 61 324 7944 Sloan Simpson +1 862 778 5052

Pierre-Michel Bringer

Thomas Hungerbuehler 

Isabella Zinck

+41 61 324 1065

+41 61 324 8425

+41 61 324 7188

Cory Twining +1 862 778 3258

source: https://www.csrwire.com/press_releases/43701-Novartis-and-DNDi-to-Collaborate-on-the-Development-of-a-New-Oral-Drug-to-Treat-Visceral-Leishmaniasis?tracking_source=rss

[thatssorue]

Keeping parasites from sticking to mosquito guts could block disease transmission

Infections such as Chagas disease, African sleeping sickness, and leishmaniasis are caused by a group of microorganisms called kinetoplastids. In a new study, a research team used a non-disease-causing kinetoplastid to investigate how these parasites adhere to their insect hosts' insides. Their findings could help in the development of targeted therapies that prevent insects from transmitting these diseases to humans. from Nature's Incredible! https://ift.tt/2KbEKEF via Nature & Insects

[ruggerorespigo]

Keeping parasites from sticking to mosquito guts could block disease transmission

Infections such as Chagas disease, African sleeping sickness, and leishmaniasis are caused by a group of microorganisms called kinetoplastids. In a new study, a research team used a non-disease-causing kinetoplastid to investigate how these parasites adhere to their insect hosts' insides. Their findings could help in the development of targeted therapies that prevent insects from transmitting these diseases to humans. Latest Science News -- ScienceDaily https://www.sciencedaily.com/releases/2019/07/190730125257.htm

[avianmalaria]

Correlates of blood parasitism in a threatened marshland passerine: infection by kinetoplastids of the genus Trypanosoma is related to landscape metrics of habitat edge.

http://dlvr.it/R4MhFh

[secretofpet]

best: Exotic signaling mechanism in pathogens — ScienceDaily

//pagead2.googlesyndication.com/pagead/js/adsbygoogle.js

(adsbygoogle = window.adsbygoogle || []).push({});

Today –

The unicellular parasite that causes sleeping sickness differs from other eukaryotes in the mode of regulation of an essential cellular signaling pathway. This provides a promising point of attack for drug development.

Trypanosoma brucei — the insect-borne eukaryotic parasite that causes sleeping sickness in tropical Africa — is the best known representative of a group of unicellular organisms known as kinetoplastids. Species belonging to this group are responsible for a number of potentially lethal infections in humans and other mammals, which are difficult to treat effectively. These include the trypanosome T. cruzi — the causative agent of Chagas disease, which is endemic to much of South America, while members of the related genus Leishmania attack the skin and mucous membranes. Leishmaniasis is a largely tropical disease, but is also found in Southern Europe. Research carried out by Ludwig-Maximilians-Universitaet (LMU) in Munich geneticist Professor Michael Boshart´s team with lead author Dr. Sabine Bachmaier and collaborators has now revealed that, in T. brucei, an essential intracellular signaling pathway is regulated differently from what has been established as a paradigm in eukaryotes. This discovery reveals a potential vulnerability, which could provide a promising target for new and specific therapies for infections caused by kinetoplastid parasites. The findings appear in the online journal Nature Communications.

Protein kinase A (PKA) is an enzyme found in virtually all nucleated (eukaryotic) organisms apart from plants, and it plays a crucial role in cellular responses to external signals. In almost all eukaryotes, the enzymatic activity of PKA is dependent on binding of the molecule cAMP, which binds to the regulatory subunit of the protein. PKA is also essential for the survival of Kinetoplastida, as it has been shown to target cell division, cell motility and development in the group. However, all efforts to demonstrate a link between cAMP and PKA activity have failed. “We have known for several years that the PKA found in T. brucei cannot be activated by cAMP, but there have been several contradictory reports in the published literature,” Boshart explains. “We have now comprehensively and conclusively verified this unexpected finding experimentally.”

To do so, the researchers developed an experimental test that allowed them to detect PKA activity in living trypanosomal cells. As in their earlier test-tube experiments, they found that there was no change in PKA activity when the intracellular level of cAMP was altered by chemical or genetic means. “In collaboration with a chemist who works for a small company, we tested an array of chemical compounds which we had identified as possible alternative regulators of the kinase enzyme, based on our experimental data,” Boshart says. The search identified a number of candidate molecules that were able to activate the typanosomal PKA. “We then chose the most effective candidate from this set and optimized its performance by appropriately modifying its chemical structure,” says Boshart. In this way, we obtained a compound that acted as a specific and highly potent activator of the enzyme.”

With the aid of 3-D structural analyses, they went on to show that the activator binds to the trypanosomal enzyme at the site in the regulatory subunit to which cAMP binds in PKAs from other eukaryotes. However, the detailed architecture of the binding pocket differs between the two proteins. The differences involve only two or three amino acid substitutions, but these changes suffice to ensure that cAMP no longer fits — while the synthetic alternatives fill the cavity neatly.

With these alternative activators, Boshart and his colleagues now have useful tools at hand with which to probe the function(s) of PKA in the Kinetoplastida and identify the enzyme’s target proteins. In addition, the results are of great interest from the therapeutic point of view. With appropriate modification, the parasite-specific activator could possibly be converted into an inhibitor of the trypanosome’s PKA, without affecting the function of the mammalian host’s enzyme.

Story Source:

Materials provided by Ludwig-Maximilians-Universität München. Note: Content may be edited for style and length.

//pagead2.googlesyndication.com/pagead/js/adsbygoogle.js

(adsbygoogle = window.adsbygoogle || []).push({});

Subscribe To Our Newslatter

First name

Email *

http://secretofpet.co.place/best-exotic-signaling-mechanism-in-pathogens-sciencedaily/

from Secret Of Pet All Goods For Our Friends

[randybenedict]

Targeting thymidylate biosynthesis in kinetoplastid and apicomplexan protozoans

Kinetoplastid and apicomplexan parasites include protozoans which are responsible for human diseases, and cause a serious impact on human health and the socioeconomic growth of developing countries. Chemotherapy is the main option to control these pathogenic organisms. from The Medical News http://bit.ly/2ELFwHc