the next webinar promoted by the Academy of Sciences of the State of São Paulo (ACIESP), with the participation of Edvaldo Vilela (President of CNPq) and Hugo Aguilaniu (Director-President Serrapilheira ).

YouTube Live Stream:

https://youtu.be/eNrBtJFTDmg

Also with the panelists: Vanderlan Bolzani (P4resident of ACIESP), Paulo Artaxo (Vice President of ACIESP) and Adriano D. Andricopulo (Executive Director of ACIESP)

Thursday, 05/27, at 4 pm

Live streaming on YouTube:  https://youtu.be/hor7ApMDfBM

The results of the research, carried out with support from FAPESP, were published in the journal ACS Central Science, of the American Chemical Society.

“We had the opportunity to sample anthills in several Brazilian regions, including the Amazon, the Atlantic Forest and the transition section from this one to the Cerrado. What caught our attention the most was the wide geographic distribution of attinimycin, present in 73% of the bacteria associated with leaf-cutting ants collected in Brazil. This fact suggests that the substance has a relevant ecological role ”, says Monica Tallarico Pupo, professor at the Faculty of Pharmaceutical Sciences of Ribeirão Preto at the University of São Paulo (FCFRP-USP) and coordinator of the research alongside Jon Clardy, from Harvard University (U.S).

As Pupo explains, leaf-cutting ants maintain multilateral symbiotic relationships with various microorganisms that inhabit the anthill and this guarantees them food and protection. The leaves that the insects carry into the nest serve as a substrate for cultivating fungi of the species Leucoagaricus gongylophorus, which they use to eat. And farm ants also feed bacteria of the genera Pseudonocardia and Streptomyces, which in turn produce compounds that act as “agricultural pesticides”, keeping the fungus garden free of pathogenic species.

“Symbiotic bacteria produce compounds capable of killing the parasitic fungus without harming the food source. Our goal was to find out what these compounds are and whether they had the potential to treat diseases that affect humans, ”says Pupo.

The project was conducted between 2014 and 2020, under the BIOTA-FAPESP Program and under an agreement signed with the National Institutes of Health (NIH) in the United States. During this period, in addition to attinimycin, the group identified an antifungal molecule named kyphomycin and substances belonging to the pyrazines class – also produced by symbiotic bacteria -, which help leaf-cutting ants to locate themselves when they leave the nest in search of leaves (read more at agencia.fapesp.br/29958/ and agencia.fapesp.br/27328/).

Experiments

The first stage of the recently published work involved analysis of metabolomics. Using techniques such as chromatography and mass spectrometry, scientists identified the entire set of metabolites produced by isolated bacteria in anthills of different Brazilian biomes.

“We noticed that the same compound – hitherto unknown – was present in almost all samples, something rare and unexpected. We then decided to investigate this molecule further. Attinimycin has a structure similar to that of already known compounds, but the amino acid sequence that forms this compound has never been described before ”, says Pupo.

The next step was to characterize, in the genome of the bacterium Pseudonocardia spp., The group of genes responsible for the synthesis of attinimycin. Based on the results, the researchers designed primers (small fragments of DNA complementary to the genetic material to be studied) that allowed to evaluate whether this same group of genes was present in symbiotic bacteria from other species of leaf-cutting ants.

A large collection was evaluated, which included samples collected by employees in Panama. However, the attinimycin genes were only found in the symbionts of the Brazilian lineages. “This finding raised the hypothesis that during the evolutionary process of these insects there was a differentiation, since this ability to produce attinimycin is related to the evolution of the Brazilian symbiotic strains”, says Pupo.

After characterizing the molecule in the laboratory, the group coordinated by Pupo returned to one of the places where the initial samples had been collected: Itatiaia National Park (RJ), in Serra da Mantiqueira. The objective was to find out if attinimycin was actually being produced in the natural context in which ants and their symbionts live. In the previous experiment, the bacteria had been grown in the laboratory, and the metabolites were extracted from that culture in vitro.

“This second time, we did the extraction of the metabolites at the collection site, to then analyze by mass spectrometry and see the chemical substances there. We detected attinimycin in about 40% of the samples. This shows that the compound must have an important role in this symbiotic system ”, says the researcher.

In the laboratory, says Pupo, attinimycin inhibited the growth of the Escovopsis fungus, a pathogen of leaf-cutting ants, which suggests its protective role in the natural environment.

The experiments were conducted by FAPESP doctoral fellow Taise Fukuda and postdoctoral fellow Weilan Melo.

Therapeutic effect

The antifungal action of attinimycin was tested by North American collaborators in mice infected with Candida albicans, which in humans can cause damage to several tissues, mainly in the oral and vaginal mucosa, urinary and gastrointestinal tract. The treatment effect was compared to that of antifungal drugs already used in the clinic (azole class), among them fluconazole. According to the researchers, the activity of attiminicina was equivalent to that of the drugs already available. The advantage is that, because it is a new molecule, microorganisms have not yet developed resistance mechanisms.

“Attinimycin has significant antifungal activity, but it still lacks an adequate chemical structure to become a drug. The idea is that it serves as a model for the design of new drug candidates and for us to better understand the mechanism of action of these drugs ”, explains Pupo.

The article Specialized Metabolites Reveal Evolutionary History and Geographic Dispersion of a Multilateral Symbiosis can be read at https://pubs.acs.org/doi/abs/10.1021/acscentsci.0c00978?source=cen%20no

CIBFar is a FAPESP Research, Innovation and Dissemination Center (CEPID) based at the São Carlos Institute of Physics of the University of São Paulo (IFSC-USP).

The fellow will perform the activities at a distance, with occasional face-to-face meetings with the responsible teacher, however, it will be necessary to manage the team using software such as Redmine or similar.

The grantee’s activities include: coordinating the design, planning and execution of responsive web games; manage a team of about ten scholarship students from USP, assigning responsibilities and guiding tasks; coordinate students’ synchronous and asynchronous communication using tools such as Slack or similar; capture and manage project information using Gdrive file management and other Google tools; and manage code versioning using GitHub.

The candidate must have knowledge of game design, modeling by Blender, development on the Unity engine or frameworks such as React and the like.

Those interested in applying should contact the responsible professor Leila Maria Beltramini, by e-mail  leila@ifsc.usp.br.

More information about the vacancy at: www.fapesp.br/oportunidades/4241

The selected TT-4 fellow will receive a FAPESP Scholarship for technical training in the amount of R $ 3,104.80 without a job, for two years, with a dedication of 40 hours per week to activities supporting the research project. A period of weekly dedication in the home office is accepted.

More information about FAPESP’s Technical Training scholarships: www.fapesp.br/bolsas/tt

Link to original article:  https://agencia.fapesp.br/centro-de-pesquisa-e-inovacao-em-biodiversidade-e-farmacos-oferece-vaga-de-treinamento-tecnico/35804/

CIBFar is a FAPESP Research, Innovation and Dissemination Center (CEPID) at the São Carlos Institute of Physics of the University of São Paulo (IFSC-USP).

Post-doctoral students will develop their activities according to the following methodologies: amplification, cloning, recombinant expression and purification of SARS-CoV-2 proteins and circulating arboviruses in Brazil and relevant as potential targets for antiviral drugs; development and standardization of activity or binding assays for the expressed recombinant enzymes, used in the selection of specific ligands and inhibitors; crystallization and, in positive cases, collection of diffraction data and resolution of the respective structures for subsequent development of specific ligands using fragment screening and cocrystallization methodologies; and biochemical / biophysical screening of compounds and planning of antiviral molecules.

Candidates must have a good academic record and full training in the methodologies applied in the research.

Interested parties should send a Lattes curriculum and a brief description of their interest in the line of research to Professor Glaucius Oliva (oliva@ifsc.usp.br), CIBFar coordinator.

More information about the vacancies at:

www.fapesp.br/oportunidades/4215 and www.fapesp.br/oportunidades/4216

Postdoctoral opportunities are open to Brazilians and foreigners. Those selected will receive a postdoctoral fellowship from FAPESP in the amount of R $ 7,373.10 per month and a Technical Reserve equivalent to 10% of the annual scholarship amount to meet unforeseen expenses and directly related to the research activity.

If the PD scholarship holders live at home outside the city in which the research institution is located and need to move, they may be entitled to an installation allowance. More information about the FAPESP Postdoctoral Scholarship is available at www.fapesp.br/bolsas/pd

Link to original article:  https://agencia.fapesp.br/centro-de-inovacao-em-biodiversidade-e-farmacos-abre-duas-vagas-de-pos-doutorado/35731/

“Biomolecules: theoretical bases and teaching methodologies”,

to teachers from public basic schools, DRE-São Carlos-SEE-SP from natural science areas.

The course was conducted from June until December/2019, with the support of graduate students and Pós docs of CIBFar for the practical tutorial classes.

Prof. Nelma R.S. Bossolan and Educator Gislaine C. dos Santos.
Specialization course taught by CDCC-SC-USP, 2019/2020:

“Methodology of the Teaching of Natural Sciences”.

Discipline: Current Topics in Science Education.

Prof. Leila Maria Beltramini and Educator Gislaine C. Santos.

Elective class denoted “Conde Medicinal Garden”, to high school students from
Escola Estadual Conde do Pinhal”, initiated in February/2020. The class was
paralyzed as a function of pandemic.

Subscription:   https://www.sympla.com.br/abc–covid-19-e-a-inovacao-de-farmacos-no-brasil–webinarios-da-abc-ed-19__931772

Date: Tuesday, 11/8/2020 

Time: 16h (GMT-3)

Facebook Event: FanPage

Local:  http://www.abc.org.br/transmissao

The São Paulo State Academy of Sciences (ACIESP) holds another event in the series – ACIESP webinars – with the participation of Patricia Ellen da Silva, Secretary of Economic Development, Science and Technology of the State of São Paulo, and Marco Antonio Zago, President of FAPESP.

Participations also by Vanderlan da Silva Bolzani, Paulo Eduardo Artaxo Netto and Adriano Defini Andricopulo.

Date: July 9, 2020 – Thursday

Time: 2:30 pm

Location: Live streaming on YouTube:  https://youtu.be/-bLEnC6Wq9s

Webinar with Dr. Drauzio Varella, Prof. Dimas Covas, Prof. Adriano D. Andricopulo and journalist Herton Escobar on the development of medicines and vaccines for Covid-19 and the health challenges in Brazil.

When :             06/10/2020  –  from 16:00h to 18:00h

Where:            Online

To more informations:    http://www.iea.usp.br/eventos/SW-desafios-em-saude-no-brasilPara

To access the webinar:    http://www.iea.usp.br/aovivo

The idea is to search, in different repositories and databases, for chemical compounds capable of blocking the action of the so-called “non-structural proteins” of the new coronavirus (SARS-CoV-2), essential for the replication of the microorganism within the human cell.

“When the virus enters the cell, it starts making copies of its own genetic material [in the case of SARS-CoV-2, an RNA] so that it can multiply and advance through the infected organism. A part of the viral genome produces proteins on the surface of the virus and also 16 other non-structural proteins, which only appear after the cell is invaded. These molecules are responsible for replicating the viral genome. Our goal is to find a compound that ‘sticks’ to one of these non-structural proteins and thus makes replication of SARS-CoV-2 unfeasible”, says Prof. Glaucius Oliva, coordinator of CIBFar, a Research, Innovation and Diffusion Center (CEPID) supported by FAPESP at the São Carlos Institute of Physics of the University of São Paulo (IFSC-USP).

The multidisciplinary project, supported by FAPESP, also brings together researchers from the Institute of Biomedical Sciences (ICB-USP), from the São Carlos  Institute of Chemistry (IQSC-USP), from the School of Pharmaceutical Sciences of Ribeirão Preto (FCFRP-USP), from Paulista State University (Unesp) and the University of Campinas (Unicamp).

Two screening processes

The selection of compounds is being carried out in two different ways. One is virtual screening – through computational techniques, such as artificial intelligence, and experimental, such as crystallography -, which aims to analyze the three-dimensional structure of molecules. The goal is to verify among the analyzed compounds which have a chemical structure capable of fitting the target (the non-structural proteins of the new coronavirus) and, therefore, potential to prevent viral replication

The second way of selection involves experimental tests to evaluate the molecules ability to inhibit the enzymes involved in the replication process. This is only possible thanks to the recombinant production of viral enzymes in CIBFar, among them the main protease of SARS-CoV-2 known as Mpro (enzyme that breaks down RNA coding proteins).

“We have already managed, for example, to produce the protease Mpro at CIBFar and we are carrying out inhibition tests with natural and synthetic compounds. The virus needs this enzyme to cut the long chain of proteins encoded by its genome. Then, each part of this chain will fold up and compose the replication complex”, explains the researcher.

Molecules with the ability to inhibit enzymes will be validated in invasion and infection assays of human cells by the new coronavirus obtained from viral isolates from Brazilian patients, performed at ICB-USP. “Whatever works, whether in the virtual assay or in the enzymatic assay, will need to be confirmed in in vitro tests, only to then move on to animal tests and, finally, clinical trials on patients. Invariably, developing new drugs is a time-consuming process until its effectiveness and safety are certain ”, he says.

Biodiversity wealth

For Prof. Oliva, a differential of the project lies in the screening of natural products from Brazilian biodiversity, mainly due to the existence of the database of the Nucleus of Bioassays, Biosynthesis and Ecophysiology of Natural Products (NuBBE-DB), which gathers information on the structure of more than 54 thousand natural molecules. The repository was developed with support from CIBFar.

“Of course, a molecule that has never been used as a drug before can take five to 10 years to prove its effectiveness and safety. However, we have something different in Brazil: access to natural products and the use of extracts known to traditional culture”, he says

As the researcher explains, plants and microorganisms are important sources of medicinal compounds. Because they do not have an immune system or much mobility, they use chemical compounds as the main weapon against predators or invaders. “This means that, over millions or billions of years [in the case of bacteria and fungi], by natural selection, it was possible to develop synthetic ways to produce protective molecules. As we have a great biodiversity in Brazil and an important previous work of identification, characterization and cataloging of these compounds, it may be that compounds come from natural products capable of inhibiting the action of the new coronavirus ”, he says.

Diversified fronts

The project also aims to guide the repositioning of drugs already approved for human use. The researchers will evaluate 1,500 compounds already approved by the FDA (Food and Drug Administration, an agency that regulates drugs in the United States) and, depending on the capacity of the cellular assays at ICB-USP, they will be able to access thousands of compounds from the organization’s libraries international Medicines for Malaria Ventures (MMV) and several other collections of projects that are under development in the State of São Paulo.

According to Prof. Oliva, the process of developing new drugs tends to be shortened when molecules of existing drugs – which have already passed all the necessary safety tests – are analyzed for other indications. “These will be the first molecules to be tested, even though the examples of successful drug repositioning are very rare,” he says.

Link to original article:   http://agencia.fapesp.br/pesquisadores-buscam-moleculas-antivirais-para-tratamento-da-covid-19/33270/