Topics:

• Basic optics, light phenomena, objective lenses and resolution.
• Wide field techniques; phase contrast, dark field and DIC.
• Fluorescence and confocal microscopy.
• 3D and live imaging.
• How to assemble figures for publications.
• Sample preparation.
• Practical sessions with microscopes.

The presence of coronavirus viral particles in red blood cells could facilitate the spread of the disease and be a pathway for systemic invasion throughout the body, beyond the respiratory system as previously believed.

This is one of the conclusions of a study carried out by researchers from the Institut Pasteur de Montevideo, the Faculty of Sciences (Udelar) and the University of Buenos Aires (UBA), published in the scientific journal Cell Death and Disease, part of the Nature group.

The finding suggests that hemoproteins (a type of protein present in red blood cells that, among other things, serve to transport oxygen to the blood) could facilitate viral dissemination. On that basis, the scientific team estimates that in patients with covid-19, the severity of the disease could be reduced through treatments that target hemoproteins. ‘Our findings propose a paradigm shift in the therapeutic approach, taking advantage of the virus-heme interaction as a strategic hinge for intervention’, the study indicates.

Understanding the mechanism

The research emerged to gain a better understanding of the mechanisms of coronavirus spread, which are still not fully understood. ‘The ability of the virus to navigate between cell and cell, tissue and tissue, and therefore cause organ failure in some cases, is still a question that is not fully understood’, said researcher Gonzalo Moratorio, who was part of the study.

The scientific team explored the effects the virus has on the body by combining clinical observations from autopsies of patients with covid-19 with data from infected mice. Specifically, a type of coronavirus that naturally infects mice was used to look for points of comparison with SARS-CoV-2 that affects humans. They arrived at the results thanks to the combination of several techniques and the collaboration of researchers from Uruguay, Argentina and Canada.

These findings help provide a more complete understanding of how the coronavirus acts and what potential treatments for patients might be. ‘Our findings propose a paradigm shift in therapeutic approaches, leveraging the virus-heme (virus and blood) interaction as a strategic hinge for intervention’, the study states.

The full study can be read here.

Researchers from the Institut Pasteur de Montevideo and the Feinstein Institutes for Medical Research (USA) have identified a key protein linked to vascular anomalies (such as arteriovenous malformations) characteristic of a rare genetic disease that affects around 800 people in Uruguay and so far has no cure.

As part of the study -published in the scientific journal Nature Cardiovascular Research-, the scientific team also tested two drugs that, in the medium term, could be used to treat the pathology.

This is Hereditary Hemorrhagic Telangiectasia (HHT), a disease that affects the blood vessels, and in extreme cases can be fatal. Sufferers develop certain arteriovenous malformations, which cause abundant bleeding from the nose and gastrointestinal tract, which, in the long term, can lead to anemia. Arteriovenous malformations (abnormal connections between arteries and veins) can affect the brain, liver and/or lungs and, depending on the organ affected, lead to complications that can be very serious and even fatal.

The arteriovenous malformations of HHT occur, among other things, because the cells of the blood vessels lose control and begin to multiply uncontrollably. The mechanism is similar to that which occurs in some types of cancer, when the cells lose control, proliferate uncontrollably and grow in size, forming a tumor.

In tests on mice, the research team found that, in the case of HHT, the CDK6 enzyme (a protein involved in the control of cell division) is responsible for this dysregulation.

During the tests they found that, in mice lacking the enzyme, they did not experience arteriovenous malformations and, therefore, did not develop the pathology.

Other studies have already evaluated the involvement of CDK6 in breast cancer, for example. Therefore, thinking of a future application in humans, the team looked for existing drugs that inhibit the action of the enzyme. In particular, they tested in mice with HHT two drugs used to treat oncology patients: Palbociclib and Ribociclib. In these tests, they observed that the HHT animals that received the medication reversed the arteriovenous malformations.

“In the medium term, drugs of this type could be used to treat HHT in humans. It is going to take several years of research and some punctual trials for patients to finally be able to use them as therapy,” said Santiago Ruiz, a researcher at the Laboratory of Metabolism and Aging Pathologies of the Institut Pasteur in Montevideo, who was part of the study.

“There is also the possibility that these drugs could be used in other diseases in which arteriovenous malformations occur whose development depends on CDK6 upregulation,” he added.

HHT in the world

Worldwide, the disease has a low prevalence (which is why it is classified as a “rare disease”) of one case per 5,000 people. Given the small number of cases, the general lack of knowledge makes diagnosis and treatment difficult. So far, HHT has no cure, and only palliative treatments are available.
Ruiz, in collaboration with other members of the Institute’s Laboratory of Metabolism and Aging Pathologies and physicians from the Pereira Rossell and Maciel Hospitals, have been studying the disease for several years.

The full study can be read here.

Luis Barbeito, a scientist with a long career in neurosciences, founder and former director of the Institut Pasteur de Montevideo, is the winner of the Gran Premio Nacional de Ciencias 2024, awarded by the Ministry of Education and Culture every three years since 2021.

The award highlights the scientific work of Uruguayan researchers and, based on nominations from colleagues, evaluates the production of knowledge, the training of human resources and the contribution to institution building.

The jury, composed of the Minister of Education and Culture, a member of the National Council for Innovation, Science and Technology and representatives of the academies of Science, Engineering, Medicine and Veterinary Medicine, highlighted several of Barbeito’s achievements in different areas.

According to the award certificate, Barbeito has had an outstanding career as a leader of neuroscience research groups focused on the chemistry of excitatory amino acid-mediated neurotransmission and on the role of glial cells in the progression of neurodegenerative diseases, particularly amyotrophic lateral sclerosis. He also points out that Barbeito has introduced new research models in neuroscience to deepen the knowledge of the cellular mechanisms that lead to progressive neuronal death and, at the same time, to devise new therapeutic interventions aimed at halting the progression of the neurodegenerative process. In this regard, according to the minutes, the patents generated on new therapeutic agents to combat these ailments are irrefutable evidence.

A focus of his work has been the understanding of astrocyte transformation processes from cells that at the physiological level provide trophic support to neurons to mediators of neurotoxicity and neuronal death in pathologies of the nervous system. In addition, he and his colleagues have investigated the interaction of neural cells with immune cells such as mast cells, neutrophils and myeloid precursors, as well as the role of cellular senescence.

The jury also valued the awards received by Barbeito throughout his career, from the Claude Bernard Award of the Franco-Uruguayan Medical Association in 1984, his appointment as a full member of the Academies of Sciences and Medicine, and the Doctor Honoris Causa of the Faculty of Medicine, University of the Republic, awarded in 2024.

He also highlighted his scientific production, which includes more than one hundred peer-reviewed publications in renowned journals, as well as book chapters in his field of research.

Along with this work, Barbeito has also dedicated himself to the training of human resources in neurobiology, not only through his teaching activity at the School of Medicine, but also through the 19 Master’s theses and 12 PhD theses completed under his guidance.

In addition to these contributions, the jury highlighted Barbeito’s fundamental work in national academic institutions. For example, in his extensive career he has been president of the Board of Directors of the Instituto de Investigaciones Biológicas Clemente Estable (1996-1999 and 2003-2005), president of the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICyT) (2005-2008) and executive director of the Institut Pasteur in Montevideo.

Biographical summary

Barbeito, who graduated from the School of Medicine of the Udelar in 1982, began his interest in neurobiology research as an assistant in the Department of Histology and Embryology (1978-1981). He then joined the Instituto de Investigaciones Biológicas Clemente Estable (IIBCE), where he continued his research and became head of the Department of Cellular and Molecular Neurobiology until 2010. Between 1985 and 1989, he completed a specialization in Neuropharmacology at the Collège de France (Paris), which laid the foundations for his future lines of research in the area of Neurochemistry. In 2005 he joined the Pasteur Institute in Montevideo as scientific director and head of the Neurodegeneration Laboratory. From 2008 to 2018 he served as executive director of the institution.

In 2024 he finished his work at the head of the laboratory, but he continues to be linked through Xeptiva, a start-up incubated at the institute that, based on the results of the pain-related research carried out at IP Montevideo, has focused on developing products for use in pets to treat diseases whose common denominator is chronic inflammation.

LAB+ Company Builder, the initiative created by the Institut Pasteur de Montevideo and Ficus Advisory that drives scientific start-ups to become global enterprises, announced the opening of a new international call.

The call is for scientists with an original, disruptive and innovative project with outstanding commercial potential.

More information: bit.ly/labpluscall

LAB+,the company builder of the Institut Pasteur de Montevideo, is calling for applicants to fill the position of Valorization Assistant with a workload of 40 hours per week from Monday to Friday, on-site.

Training attained and skills

We are looking for advanced students or recent graduates of careers related to management, administration, accounting and/or finance.

Training and knowledge in the following areas will be especially valued:

• Advanced proficiency in spreadsheets (Excel) and Microsoft Office suite (required).
• Administrative management of companies and/or institutions
• Management software, accounting, ERP, or similar.
• Costing of services and products
• Accounting and Cash Flow knowledge, with an ability for numbers.
• Management of Business Intelligence programs (e.g. Power BI).
• Basic knowledge on Marketing and Valuation Models
• Good level of English (spoken and written)
• Very good communication skills (both spoken and written).

Experience

The person must have work experience in Management, Commercial, Financial and/or Reporting positions.

Responsibilities

The selected person will perform tasks related to the management and monitoring of the start-up portfolio linked to the institute.

Will support the costing of the institute’s services, as well as their valorization (budgeting, follow-up, marketing, etc.). He/she will also provide support in the preparation of contracts of valorization (commercial or partnership).

Will receive and handle requests from internal and external clients (primarily in Spanish and occasionally in English), and will interact with other corporate counterparts (both national and international), institutional entities, and other organizations and agencies.

Will collaborate with the filing of documentation and the preparation of reports related to the tasks detailed above, and will provide general support in tasks of their competence, among other responsibilities.

Other requirements

In addition to the required training, we are looking for a proactive person, with analytical and attention to detail mentality, methodical and logical approach, with good interpersonal, communication and collaboration skills.

We are looking for an executive profile, with autonomy, initiative, curiosity, adaptability and flexibility, organization and good time management to meet deadlines, as well as commercial knowledge and a business vision.

Duration

The duration of the position is indefinite, with a three-month probationary contract.

Application Process

We invite interested persons to apply through this link in .pdf format, attach resume with work references and note of interest.

Applications will be received until September 01, 2024.

In the event of any inconvenience that arises when completing the application form, we appreciate sending an email to the address: llamados@pasteur.edu.uy

The Institut Pasteur de Montevideo is an institution committed to promoting a gender-equitable organizational culture. The Institution adheres to Law No. 17,817 on combating racism, xenophobia and all other forms of discrimination and Law No. 19,846 on the obligations arising from international human rights law, in relation to equality and non-discrimination between women and men, including formal, substantive and recognition equality.

Under this legal framework, and in compliance with Article 8 of Law No. 19,846 on Special Temporary Measures, every effort will be made to ensure that the applications are evaluated by a gender parity commission with training in the subject, and in the event of an equal background between two candidates of different genders, the woman will be favored.

This call is open to persons registered in the National Registry of Persons with Disabilities (Law No. 19,691), who meet the conditions and suitability for the position.

The Chronic Lymphoid Leukemia Research Laboratory (iLLC) of the Institut Pasteur of Montevideo is calling for applications for a postdoctoral researcher, 40 hours per week.

Qualifications:

A PhD degree by the time of appointment.

Experience

Previous knowledge in cellular and molecular biology, immune techniques as flow cytometry, Western Blot and ELISA and handling murine models, will be considered advantageous but not exclusive. Experience in the fields of immunology and hemato-oncology is also desirable.

Responsibilities

The selected candidate will lead a project directed by Dr. Pablo Oppezo, in the rLLC laboratory in collaboration with Glaxo Smith Kline (GSK) Technology and Science platform in the field of Immuno-oncology. The project will focus on understanding the molecular mechanisms of progression and therapeutic resistance in chronic lymphocytic leukemia.

The main techniques used will be flow cytometry, ELISA, confocal microscopy, quantitative PCR, and next generation sequencing. The development of the proposed project will be the primary activity of the applicant, requiring a high level of dedication to this task.

Reference Salary:

As of September 2024, the nominal salary for the postdoc position is 110,490 Uruguayan pesos, (2800 USD).

Communication of results

It is expected that results will be announced before November 6, 2024, although this depends on the number of applicants and the characteristics of the applications.

Duration

The position will last for 2 years, with the possibility of extending the position for a period of up to 18 or 24 months, through competitive funding.

We invite interested persons to apply through the following link by attaching the following documentation in .pdf format:
a) Letter of motivation

b) Two academic letters of recommendation.

c) Curriculum vitae summarized containing the following information:
– Personal Data
– Academic Background
– Scientific work history
– List of publications
– Oral presentations at congresses
– Scientific awards and/or scholarships

The deadline for receipt of applications is Monday, September 23, 2024. Monday, September 23, 2024.

The Institut Pasteur de Montevideo is an institution committed to promoting a gender-equitable organizational culture. The Institution adheres to Law 17.817 on combating racism, xenophobia, and all forms of discrimination, as well as to Law No. 19846 on the obligations emerging from international human rights law regarding equality and non-discrimination between women and men, encompassing formal, substantive, and recognition equality.

Under this legal framework, and in compliance with Article 8 of Law No. 19846 on Special Temporary Measures, we will make every effort to ensure that applications are evaluated by a gender-balanced commission with expertise in the topic. In the case of equal qualifications between two candidates of different genders, preference will be given to the female candidate.

The Institut Pasteur de Montevideo is looking to expand its scientific team through an open call for two postdoctoral researchers to develop research projects aligned with current institutional scientific priorities (no prior affiliation with the institute required).

Training attained

Candidates must have completed their PhD between 2019 and March 31, 2025. While this is the preferred profile, applications that do not strictly meet these criteria but are adequately justified will also be considered. For candidates who have experienced maternity, an additional year will be accepted for the PhD completion (2018) per child born or adopted after obtaining the doctorate, and up to 2 additional years (2017) for multiple children born or adopted after obtaining the doctorate. Other justified circumstances such as illnesses or caregiving responsibilities will also be considered.

Duration

The position is for a duration of 2 years, potentially renewable once for up to 18 months. In the case of maternity during the contract period, deadlines will be extended by 9 months.

Salary reference

As of July 2024, the nominal salary for the postdoctoral position at IP Montevideo is $110,490 Uruguayan pesos.

Application Process

Interested individuals should contact the responsible heads of the Technological Units or Research Laboratories of interest (contacts available on the institute’s website) to assess candidacy feasibility and to develop a work plan. The development of the proposed project should be the main activity of the applicant, requiring high dedication to this task.

Interested parties are invited to submit the following documents in PDF format in Spanish or English:

a) Curriculum vitae using the specified biosketch format.

b) Work plan (1,000 words) including:
-Project title
-Laboratory or unit where the postdoc will be conducted. If it’s a collaborative project, clearly identify the main affiliation.

-Background and rationale, objectives, and work plan (considering the position’s 2-year duration, extendable by 18 months).

c) Annex, if applicable, where references, figures, and tables can be included.

d) Letter of recommendation from the head of the unit/lab justifying the impact of the candidate’s incorporation into the research team and the availability of funds to support the project.

Evaluation

Projects will be evaluated by an advisory committee composed of researchers from IP Montevideo. This committee will be appointed by the institute’s directors in consultation with the Academic Advisory Council, aiming to minimize conflicts of interest. Projects should be written to be understood by researchers with general training in life sciences, though not necessarily in all proposed research lines.

For any inquiries regarding the call, please contact academic@pasteur.edu.uy.

Communication of results

It is expected that results will be published before November 30, 2024, although this depends on the number of applicants and the characteristics of the applications.

Assuming the position

In 2025, to be arranged between the institute’s directors, the responsible person from the group, and the selected candidate. If a candidate selected at the time of the result has not yet defended their doctorate, they must do so by March 31, 2025, unless exceptional circumstances justify an extension. Otherwise, they will have to forfeit the position, and it will be awarded to the next candidate in priority.

Submit applications through this form, including the following information:

Email: This will be used for communication related to this call
Call number: 20-24
Call name: Institutional Postdoctoral Positions

The deadline for submissions is extended until October 22, 2024, at 17:00 h.

The Institut Pasteur de Montevideo is committed to promoting an organizational culture with gender equity. The Institution adheres to Law 17.817 against racism, xenophobia, and all forms of discrimination, as well as Law No. 19846 regarding obligations arising from international Human Rights law, ensuring equality and non-discrimination between women and men, encompassing formal, substantive, and recognition equality.

Under this legal framework and in compliance with Article 8 of Law No. 19846 on Special Temporary Measures, every effort will be made to ensure applications are evaluated by a gender-balanced committee with expertise in the field. In cases where candidates of different genders have equal qualifications, preference will be given to women.

A project led by researchers from the Institut Pasteur de Montevideo invites the population to take part in the first study to sequence the ‘Uruguayan genome’, an initiative aimed at better understanding health and diseases in the country. To participate, individuals who donate blood at the Hospital de Clínicas (a public hospital in Montevideo) are also asked to donate a sample to contribute to the genetic knowledge of the population.

The study aims to gather around 850 samples from a representative group of the population, which will allow for the analysis and comparison of this genetic information with data stored in genetic banks from other countries. This will help identify, for example, DNA differences associated with diseases. Genomic sequencing will thus enable a better understanding of Uruguayan genetic diversity and provide baseline data that will aid future studies on its health implications.

The Uruguayan population is known to comprise indigenous, European, and African ancestries, whose mixture and historical migrations have shaped the genetic characteristics of the population. The Institut Pasteur de Montevideo has been studying these topics since 2015 through the Urugenomes project (urugenomes.org), which consisted of three phases with different objectives. One phase characterized the genomes of 30 randomly selected Uruguayans and later expanded to include dozens more to identify ancestry and aspects related to rare diseases.

Building on Urugenomes, the new project expands the number of participants to create a representative sample of the population.

To participate, candidates must be over 18 years old, donate blood at the Hospital de Clínicas, and agree to donate a small amount of that blood for the study (no additional blood draw is required). Participants will consent to their genetic information being stored in international databases for scientific use, with assurances of anonymity. In return, participants will receive a simplified ancestry report that maintains their anonymity.

The study is led by researcher Lucía Spangenberg from the IP Montevideo, with collaboration from scientists at the Universidad de la República (Udelar), Institut Pasteur in Paris, and Fiocruz de Curitiba.

Researchers at the Institut Pasteur de Montevideo are currently testing three compounds that have shown promising results for treating Hereditary Hemorrhagic Telangiectasia (HHT), a rare genetic disease that affects the shape and function of blood vessels and can be life-threatening in severe cases. On the International Day of this condition (June 23), the institute continues to advance its work towards developing a treatment for a condition that currently has no cure.

‘We are currently testing these drugs in the laboratory to definitively determine their therapeutic potential for the disease’, said Santiago Ruiz, a member of the Laboratory of Metabolic Diseases and Aging at the Institut Pasteur de Montevideo, who leads this study. They have recently started testing on endothelial cells (which line the interior of blood vessels) extracted from HHT patients and are preparing to begin trials in mice.

HHT in Uruguay

In Uruguay, it is estimated that around 800 people are affected by HHT. Globally, the disease has a very low prevalence (hence classified as ‘rare’) of one case per 5,000 people. Due to the small number of cases, lack of awareness complicates diagnosis and treatment.

It is known that this disease arises when mutations in genes affect and alter the function of certain proteins involved in controlling the shape, size, and structure of a patient’s blood vessels. Therefore, one of its manifestations is frequent nosebleeds and bleeding in the digestive tract, which can lead to anemia. Another visible symptom of the condition is the presence of dilated vessels in the skin and the mucous membrane. The disease also causes arteriovenous malformations in different organs (usually affecting the brain, liver, and/or lungs), and depending on the affected organ, it can lead to severe complications and even death of the patient.

So far, there is no cure for the disease; only palliative treatments exist. Symptoms are managed with drugs that can help stop the bleeding, for example, but do not resolve the malformation in an organ.

Therefore, Ruiz, in collaboration with members of the laboratory and doctors from Pereira Rossell Hospital and Maciel Hospital (both located in Montevideo), is dedicated to studying HHT to find a drug that can alleviate the impact of the disease and, if possible, cure it.

Drugs under study

Ruiz has been working on HHT since 2015 and developed part of his research at the Feinstein Institutes for Medical Research (US) during his training abroad.

There, Ruiz was part of a team that, among other things, focused on a drug repurposing strategy: they evaluated 700 drugs that had already been approved for use in other diseases and tested them to see if any could be used in treating HHT.

Upon returning to the Institut Pasteur de Montevideo in 2021, Ruiz continued this work focused on the five drugs that had shown the best results, aiming to analyze them in depth. He found that three of these drugs can normalize the functioning of the affected mechanism in endothelial cells that cause the disease.

‘We want to find drugs that act more specifically on the mechanism that produces the pathology to improve treatment success, provide more options for its management, and therefore improve the quality of life of patients. Although there are still several phases of research ahead, the advantage of using drugs that are already approved is that the process to use them as treatment is faster than with new drugs that have not been validated’, concluded Ruiz.