Label-free biomarker information by high-throughput holographic microscopy to support detection of cancer and neglected tropical diseases (Conference Presentation)

2019 ◽  
Author(s):  
Matthias Ugele ◽  
Christian Klenk ◽  
Dominik Heim ◽  
Stefan Röhrl ◽  
Frea Mehta ◽  
...  
Keyword(s):  
High Throughput ◽  
Neglected Tropical Diseases ◽  
Tropical Diseases ◽  
Label Free ◽  
Holographic Microscopy

scholarly journals Label-Free High-Throughput Leukemia Detection by Holographic Microscopy

2018 ◽  
Vol 5 (12) ◽  
pp. 1800761 ◽  
Author(s):  
Matthias Ugele ◽  
Markus Weniger ◽  
Manfred Stanzel ◽  
Michael Bassler ◽  
Stefan W. Krause ◽  
...  
Keyword(s):  
High Throughput ◽  
Label Free ◽  
Holographic Microscopy

scholarly journals High-Throughput Screening Platform for Natural Product–Based Drug Discovery Against 3 Neglected Tropical Diseases

2014 ◽  
Vol 20 (1) ◽  
pp. 82-91 ◽  
Author(s):  
F. Annang ◽  
G. Pérez-Moreno ◽  
R. García-Hernández ◽  
C. Cordon-Obras ◽  
J. Martín ◽  
...  
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Natural Product ◽  
High Throughput ◽  
High Throughput Screening ◽  
Neglected Tropical Diseases ◽  
Chemical Diversity ◽  
Tropical Diseases ◽  
Isolation And Characterization ◽  
Microbial Extracts

African trypanosomiasis, leishmaniasis, and Chagas disease are 3 neglected tropical diseases for which current therapeutic interventions are inadequate or toxic. There is an urgent need to find new lead compounds against these diseases. Most drug discovery strategies rely on high-throughput screening (HTS) of synthetic chemical libraries using phenotypic and target-based approaches. Combinatorial chemistry libraries contain hundreds of thousands of compounds; however, they lack the structural diversity required to find entirely novel chemotypes. Natural products, in contrast, are a highly underexplored pool of unique chemical diversity that can serve as excellent templates for the synthesis of novel, biologically active molecules. We report here a validated HTS platform for the screening of microbial extracts against the 3 diseases. We have used this platform in a pilot project to screen a subset (5976) of microbial extracts from the MEDINA Natural Products library. Tandem liquid chromatography–mass spectrometry showed that 48 extracts contain potentially new compounds that are currently undergoing de-replication for future isolation and characterization. Known active components included actinomycin D, bafilomycin B1, chromomycin A3, echinomycin, hygrolidin, and nonactins, among others. The report here is, to our knowledge, the first HTS of microbial natural product extracts against the above-mentioned kinetoplastid parasites.

scholarly journals Development of a High-Throughput Cytometric Screen to Identify Anti-Wolbachia Compounds: The Power of Public–Private Partnership

2019 ◽  
Vol 24 (5) ◽  
pp. 537-547
Author(s):  
Rachel H. Clare ◽  
Roger Clark ◽  
Catherine Bardelle ◽  
Paul Harper ◽  
Matthew Collier ◽  
...  
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Neglected Tropical Diseases ◽  
Bacterial Symbiont ◽  
Tropical Diseases ◽  
Validation Process ◽  
Host Insect ◽  
Filarial Nematodes ◽  
Development And Validation ◽  
High Throughput Assay

The Anti- Wolbachia (A·WOL) consortium at the Liverpool School of Tropical Medicine (LSTM) has partnered with the Global High-Throughput Screening (HTS) Centre at AstraZeneca to create the first anthelmintic HTS for neglected tropical diseases (NTDs). The A·WOL consortium aims to identify novel macrofilaricidal drugs targeting the essential bacterial symbiont ( Wolbachia) of the filarial nematodes causing onchocerciasis and lymphatic filariasis. Working in collaboration, we have validated a robust high-throughput assay capable of identifying compounds that selectively kill Wolbachia over the host insect cell. We describe the development and validation process of this complex, phenotypic high-throughput assay and provide an overview of the primary outputs from screening the AstraZeneca library of 1.3 million compounds.

scholarly journals The utility of yeast as a tool for cell-based, target-directed high-throughput screening

Parasitology ◽  
2013 ◽  
Vol 141 (1) ◽  
pp. 8-16 ◽  
Author(s):  
J. L. NORCLIFFE ◽  
E. ALVAREZ-RUIZ ◽  
J. J. MARTIN-PLAZA ◽  
P. G. STEEL ◽  
P. W. DENNY
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Neglected Tropical Diseases ◽  
Cost Effective ◽  
Tropical Diseases ◽  
Protein Targets ◽  
Biochemical Assays ◽  
Cost Effective Approach ◽  
Cellular Context

SUMMARYMany Neglected Tropical Diseases (NTDs) have recently been subject of increased focus, particularly with relation to high-throughput screening (HTS) initiatives. These vital endeavours largely rely of two approaches, in vitro target-directed screening using biochemical assays or cell-based screening which takes no account of the target or targets being hit. Despite their successes both of these approaches have limitations; for example, the production of soluble protein and a lack of cellular context or the problems and expense of parasite cell culture. In addition, both can be challenging to miniaturize for ultra (u)HTS and expensive to utilize. Yeast-based systems offer a cost-effective approach to study and screen protein targets in a direct-directed manner within a eukaryotic cellular context. In this review, we examine the utility and limitations of yeast cell-based, target-directed screening. In particular we focus on the currently under-explored possibility of using such formats in uHTS screening campaigns for NTDs.

Label-free, high-throughput detection ofP. falciparuminfection in sphered erythrocytes with digital holographic microscopy

Lab on a Chip ◽  
2018 ◽  
Vol 18 (12) ◽  
pp. 1704-1712 ◽  
Author(s):  
Matthias Ugele ◽  
Markus Weniger ◽  
Maria Leidenberger ◽  
Yiwei Huang ◽  
Michael Bassler ◽  
...  
Keyword(s):  
Life Cycle ◽  
High Throughput ◽  
Digital Holographic Microscopy ◽  
Ring Stage ◽  
Label Free ◽  
Life Cycle Stages ◽  
High Throughput Detection ◽  
Holographic Microscopy

Label-free, high-throughput holographic microscopy enables malaria detection at the ring stage and distinction ofP. falciparumlife cycle stages.

THE ROLE OF EBM AND CLINICAL PRACTICE GUIDELINES IN GENERATING RESEARCH AND INTERVENTIONS IN NEGLECTED TROPICAL DISEASES: A RATIONAL MODEL FOR DEVELOPING COUNTRIES

2020 ◽  
Author(s):  
Cristhian David Morales-Plaza
Keyword(s):  
Developing Countries ◽  
Clinical Practice ◽  
Clinical Practice Guidelines ◽  
Practice Guidelines ◽  
Neglected Tropical Diseases ◽  
Tropical Diseases ◽  
Rational Model ◽  
Clinical Practices ◽  
Vulnerable Communities

Guarantee better clinical practices among clinicians who attend NTDs in developing countries as well as provide education in vector control in hotspot vulnerable communities

Heterocycles in the Treatment of Neglected Tropical Diseases

2020 ◽  
Vol 27 ◽  
Author(s):  
Kush K. Maheshwari ◽  
Debasish Bandyopadhyay
Keyword(s):  
Developing Countries ◽  
Heterocyclic Compounds ◽  
Neglected Tropical Diseases ◽  
World Health ◽  
Current Status ◽  
Poor People ◽  
Tropical Diseases ◽  
Concise Review ◽  
The World ◽  
Health Organization

Background: Neglected tropical diseases (NTDs) affect a huge population of the world and majority of the victims belong to the poor community of the developing countries. Until now, the World Health Organization (WHO) has identified 20 tropical diseases as NTDs that must be addressed with high priority. However, many heterocyclic scaffolds have demonstrated potent therapeutic activity against several NTDs. Objective: There are three major objectives: (1) To discuss the causes, symptoms, and current status of all the 20 NTDs; (2) To explore the available heterocyclic drugs, and their mechanism of actions (if known) that are being used to treat NTDs; (3) To develop general awareness on NTDs among the medicinal/health research community and beyond. Methods: The 20 NTDs have been discussed according to their alphabetic orders along with the possible heterocyclic remedies. Current status of treatment with an emphasis on the heterocyclic drugs (commercially available and investigational) has been outlined. In addition, brief discussion of the impacts of NTDs on socio-economic condition is included. Results: NTDs are often difficult to diagnose and the problem is worsened by the unhealthy hygiene, improper awareness, and inadequate healthcare in the developing countries where these diseases primarily affect poor people. The statistics include duration of suffering, numbers affected, and access to healthcare and medication. The mechanism of actions of various heterocyclic drugs, if reported, have been briefly summarized. Conclusion: Scientists and pharmaceutical corporations should allocate more resources to reveal the in-depth mechanism of actions of many heterocyclic drugs that are currently being used for the treatment of NTDs. Analysis of current heterocyclic compounds and development of new medications can help in the fight to reduce/remove the devastating effects of NTDs. An opinion-based concise review has been presented. Based on available literature, this is the first effect to present all the 20 NTDs and related heterocyclic compounds under the same umbrella.

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