
In the second edition of the InnOValley Proof of Concept Fund (IOV PoC), five research projects with a potential to be transferred to industry were awarded grants. The Oeiras Valley had a chat with the winners.
Vitor Cabral, researcher from the Instituto Gulbenkian de Ciência, leads a project on a new generation of probiotics with the purpose of treating gut inflammation. From the ITQB NOVA, Margarida Archer leads a research on computationally engineered proteins for the diagnosis of emergent viruses, such as Zika virus, and for which no vaccine is currently available. Mónica Serrano, researcher at ITQB NOVA, leads the investigation on a nanoplatform for the detection of pathogens. From ITQB NOVA, Ana Pina leads a project related to the development of collagen-based biological batteries for cutaneous electronic applications. Also from ITQB NOVA, Maria Miragaia and her team are researching a new class of precision antibiotics against multidrug-resistant pneumonia.
Each of the winners will receive EUR 50,000 to confirm the preliminary data of the awarded research and to obtain new intellectual and industrial property within a period of 12 months.
Learn more about the winning projects through the words of the Faces of Science awarded for their promising research.
What results do you hope to achieve with the “next-generation” probiotic therapy in the treatment of gut inflammation?
Vitor Cabral: Our work is focused on a next-generation probiotic for the treatment of inflammatory bowel disease (IBD). Unlike classical probiotics, which are mostly obtained from fermentation processes, next-generation probiotics are bacteria native from bacterial communities living in hosts. In the specific case of our probiotic, it is a bacterium native to the intestines of mammals, including humans. The work I am developing in collaboration with Dr. Rita Oliveira, in Dr. Karina Xavier’s lab, at Gulbenkian, shows the protection that this bacterium offers in a IBD context, protecting against infections which are very common in these patients, and accelerating the recovery process of the protection that is lost when treatment is accomplished with anti-inflammatory medication or antibiotics. This funding will allow us to expand the effects of our therapy, both by studying its direct effect on inflammatory episodes, which are the root of the clinical problems that patients with these diseases suffer from, as well as studying the protective effect of our probiotic on other pathologies with that same inflammatory intestinal root, such as obesity.
Your project envisions the development of a faster and simpler alternative to PCR tests. Practically, what will this alternative consist of?
Mónica Serrano: Nowadays, diagnostic tests for infectious diseases are based on nucleic acid amplification techniques, usually PCR. This type of molecular test is extremely sensitive and its introduction in the market has revolutionized the diagnostic process by allowing the detection of infections earlier than previously possible. However, there are several limitations to the large-scale use of PCR-based molecular tests. One of the biggest limitations is the need to produce and purify the enzymes used in the tests. The cost and complexity associated with the production of these reagents is often an obstacle to continuous and large-scale surveillance before, during and after an infectious outbreak. By developing a platform for a faster and cheaper production of these reagents we will address this limitation.
Previously, the team involved in this project has developed a sensitive and low-cost test for the diagnosis of COVID-19 based on RT-LAMP. However, as per the project’s original structure, the test still relied on multi-step enzyme production and purification. Now we want to make RT-LAMP even simpler and more affordable by using Bacillus subtilis spores as a stress-resistant biocatalyst platform to detect any relevant pathogen using RT-LAMP technology. This platform uses proteins from the outermost layer of B. subtilis spores as carriers for the two enzymes used in RT-LAMP: a DNA polymerase and a reverse transcriptase (RT). The B. subtilis spore has been used successfully to display enzymes or antigens in biotechnological and biomedical applications, but it has never been used in molecular diagnostics.
How could your team’s research contribute to the diagnosis of emerging viruses like Zika?
Margarida Archer: The project will contribute to the development of diagnostic tests and vaccines against Zika (and Dengue) viruses. Through computational analysis, we will use a multidisciplinary strategy to develop proteins that contain domains only found in Zika virus (epitopes) so that they can be used in diagnostic tests mimicking human antibodies against Zika (and Dengue), which would, for their part, be used in the development of prophylactic and therapeutic vaccines. Of course, there is a long way to go if we want to reach these goals, but this grant allows us to continue our studies, together with collaborators from the Instituto Gulbenkian de Ciência and Fiocruz, in Recife.
Where did the idea of doing this research come from?
Margarida Archer: Serendipity. It is funny how science is also made of (happy) accidents. Researchers from Fiocruz came to ITQB NOVA to present their computational biology and immunology work on Flavivirus. Afterwards they interacted with several groups from ITQB NOVA. When we talked, we immediately formed a connection and started thinking how we could bring together our complementary knowledge. The project was thus “born”, and it has been developed over several years, currently with the participation of a group from the IGC as well as other partners. It is very interesting to see how bridges that narrow the distances between countries and their research can be formed. We are very excited about the Oeiras InnOValley award, it will help us to continue these studies and to achieve our goals of developing diagnostic tests and a treatment for Zika virus. This research may also extend to other Flaviviruses such as Dengue, Yellow Fever and Chikungunya.
What practical advantages for the population may the project you lead have in the future?
Ana Pina: Electronic artificial skin aims to create flexible electronic devices that mimic the functionalities of human skin. Electronic skin is commonly used in health care, robotics, and wearable electronics to monitor vital signs, muscle movements, and interactions with the environment.
Batteries are the most widely used power source for any e-skin system. Currently, there is also a need to develop fully bio-compatible battery materials since they are necessary to integrate e-skin systems. Conventional lithium batteries are rigid and composed of hazardous materials, thus compromising the safety of e-skin devices. Alternative energy sources (like biological fuel cells and enzymatic bio-batteries) are sustainable, but have limitations in terms of flexibility and elasticity. The demand for cleaner, more sustainable energy sources is a growing global concern due to rising energy costs and global warming associated with the use of fossil fuels.
Electronic skin systems self-powered by biological materials are expected to be a new contribution to a society that depends on cleaner, more sustainable and efficient energy solutions.
Our project seeks to develop an innovative ultra-thin, flexible and lightweight battery made entirely of bio-materials that mimic collagen, and thus skin functionality, and which is also capable of powering electronic skin devices for health monitoring.
The batteries proposed in the project offer a cleaner and more sustainable source of energy. The fact that these batteries are composed of peptides that mimic collagen has several advantages over traditional batteries. Since they are made from biological resources, they are environmentally friendly and environmentally sustainable, and are also built with the ideal properties to best mimic human skin. The development of batteries based on materials that mimic collagen leads to the minimization of the carbon footprint associated with energy production, thus contributing to a more sustainable future.
So far, in the research environment, what results has the new class of precision antibiotics against infections caused by multidrug-resistant Klebsiella pneumoniae bacteria shown?
Maria Miragaia: In the laboratory, we have synthesized a completely new metallic compound. We proved it has the ability to kill 99.7% of the population of multidrug-resistant Klebsiella pneumoniae bacteria tested, showing no activity against other types of bacteria. This compound is particularly promising and attractive because it is completely new, it has physicochemical properties that allow it to avoid the usual resistance mechanisms of K. pneumoniae, and it requires a simple chemical synthesis process with optimal yield and purity. Additionally, the fact that this compound has a reduced activity spectrum makes it a precision antibacterial. That means it is safer for human health – since its activity is directed at the pathogen it has a low impact on the remaining human microbiota.
In your research, what are the most advanced stages of development you hope to achieve with the grant you received?
Maria Miragaia: The awarded funding will be used to validate and characterize in detail the antimicrobial activity of the compound and to determine essential physicochemical parameters for its future production and application. In particular, we will establish the compound’s concentration that kills multi-resistant K. pneumoniae and protects benign human bacterial flora; we will identify in which bacterial cell compartment the compound is accumulated; demonstrate that bacteria are unlikely to become resistant to this compound; prove the compound’s low toxicity in human cells; and also ascertain the compound’s stability and solubility under conditions relevant to its use as an antimicrobial. These studies will allow us to design optimization strategies for the compound and to synthesize more stable and higher activity by-products. We hope that the advances achieved using this funding will allow us to patent this invention, which would attract the interest of the pharmaceutical industry and possible investors.
How important is the funding for the development of this research?
Ana Pina: This grant is fundamental for the development of the batteries proposed in the project. It will allow us to acquire the essential resources in terms of the equipment and materials needed to carry out the experimental tasks and to hire the personnel needed to advance our discoveries. This funding will allow us to develop a product with high technological impact which could revolutionize the field of electronics by creating batteries composed of sustainable materials such as peptides that mimic collagen in its structural and functional properties, and that have applications in personalized medicine and wearable electronics.
So far, what assessment would you draw from your experience in this research?
Mónica Serrano: This work began in 2020, during the pandemic. During this time, the team involved in the project developed low-cost tests for the diagnosis of COVID-19 in saliva samples. In partnership with the Municipality of Oeiras, these tests were used in early 2022 to test over 4,000 children, aged 3 to 11 years, attending school in the municipality. It was an incredible experience, where we saw science and citizenship come together. The school population was supportive of our test, helping prove its robustness, and, at the same time, it was possible to identify children, mostly asymptomatic, testing positive for SARS-CoV-2. This grant will facilitate the continuation of this team’s research to develop very low-cost molecular diagnostic tests for the detection of other pathogens.
Do you believe that the awarding of these grants is a boost for investigations like yours?
Vitor Cabral: The awarding of this grant is certainly a boost to our research, which is currently elementary. It usually falls short of studies focused on the applicability of our findings, generating scientific added-value that can later be used for more thorough and in-depth studies. But with this type of funding, we can take a step forward and invest in the applicability of our findings, studying their potential and their impact on society, thus generating added and more tangible value to our work. These initiatives are fundamental to shorten the gap between fundamental research, which is essential for scientific discovery and progress, and for the general public to have a faster and more effective access to the scientific advances made in Portugal.