The transdisciplinary character of i3S is achieved through Integrative Research Programs and by promoting projects addressing questions that require the participation of basic and applied sciences, such as:

• The development of effective and reliable in vitro diagnostic tools, namely for early detection of gastric cancer and bacterial infection, combining molecular targets and nanotechnologies, with particular emphasis on in vivo bioimaging; 
• The development of carriers, scaffolds and cell isolation, and manipulation technologies for effective cell therapies and tissue engineering strategies in neurological diseases and trauma, particularly for elderly and diabetic patients. The specific etiology of disease in these patients is often neglected but should be translated into the design of appropriate in vitro and in vivo strategies;
• The development of fundamental research to solve basic biological questions continues to be a priority and it lays the groundwork for future advancements; it is also a guiding principle in hiring new researchers.

The Cancer integrative program encompasses research groups working on Cell Division, Cell Cycle, Oncobiology, Pathology, Molecular and Cellular Biology, Cancer Genetics, and Population Genetics and Metabolism, in association with groups working on Bioengineering. This program intends to identify risk factors for cell and tissue transformation, as well as the molecular and cellular mechanisms relevant for cancer development and progression.

The groups incorporate expertise in cell cycle and cell division, a key area to understand the basis for cell transformation, growth and genetic instability. Our knowledge in pathology, molecular genetics, population genetics and genetic diversity plays a key role in furthering the understanding of the role of nuclear and mitochondrial genetic mutations in cancer. It is well known that cancer cells show changes in/loss of differentiation and, in most cases, exhibit an increase/shift in bioenergetic demand when compared to normal cells. Therefore, our groups amass expertise in metabolism, cell signaling and apoptosis, which are important to broaden our understanding on how to restrain cancer growth, to induce cell differentiation and/or to promote cell death. Additionally, we focus on the role of cell junctions, cell-extracellular matrix (ECM), and interactions of other cellular and non-cellular components of the cancer microenvironment to understand tissue architecture, cell adhesion, cell communication, migration and invasion.

We gather people with expertise in the role of adhesion molecules in cancer, such as P- and E-cadherin, that work in close collaboration with researchers working in ECM and inflammation. Since cancer "stem-like" cells possess self-renewal capability and display increased chemo and radio-resistance, their identification and modulation is important for an effective therapy and to control tumor recurrence. We use cancer patient cohorts, in vivo models and dynamic in vitro models allied to high throughput technology, bioinformatics, and state-of-the-art molecular and cellular biology to identify regulatory mechanisms and molecular circuitries, acting to confer advantageous features to pre-neoplastic and neoplastic cell populations.

Infectious diseases, impaired immune responses, and degenerative disorders are the top leading causes of death and disability worldwide. The mission of the Infection, Immunity and Regeneration (IIR) Program is to conduct groundbreaking fundamental and translational research to understand how our organism interacts with pathogens, cancer and biomaterials, and stimulates tissue repair and regeneration to develop innovative personalized anti-microbial, anti-cancer, and pro-regenerative therapies.

The Program brings together groups with complementary expertise in pathogenesis, immunity, vaccinology, clinical genetics, biomaterials, regenerative and nanomedicine, creating a unique ecosystem to tackle the aforementioned clinical challenges at the core and interface of infection, immunity and regeneration. The Program addresses these questions using multidisciplinary approaches, including advanced bioimaging, next-generation sequencing, proteomics, bioinformatics, high-content screening, nanotechnology, 3D printing and microfluidics. It benefits from rare infrastructures, including BSL2/3 facilities and bio-fabrication, and from a unique range of experimental models of human diseases, employing a series of microorganisms (virus, bacteria, parasites, fungi), in vitro cells, organ on chips, organoids and animal models (invertebrates, fish, mammals).

In the near future, the Program aims to identify and comprehend pathogen virulence mechanisms; decipher molecular processes of host immune/inflammatory responses in the context of infection, tissue repair/regeneration and cancer; identify susceptibility factors and mechanisms of microbe-induce disease; develop advanced diagnosis and anti-infective systems; and produce innovative immunomodulators and regenerative therapies.

The Neurobiology and Neurologic Disorders integrative program involves groups working on neurosciences, genetics, protein structure and regenerative medicine. It focuses on understanding the biology of neurons and glia, the causes for neuronal dysfunction and degeneration, exploring the use of biomaterials in neural regeneration and developing therapeutic strategies to ameliorate neurological conditions. The groups committed to this program enjoy international recognition, specifically on spinal networks and myelination, amyloid neuropathy, movement disorders, lysosome and peroxisome storage disorders, pain, neurourology, addiction, structural biology, axonal regeneration, design of biomaterials to improve nerve regeneration, and animal science. Cross-program interaction and external collaboration, which already took place, are now further encouraged. For instance, the interaction between epithelial cancer biology groups and groups delving into glial cell biology have been exploring the role of cell-to-cell contacts and cell-matrix interactions in the context of epithelial cancer. Additionally, groups working on gastric cancer and biomaterials have designed functionalized nanoparticles to detect and fight H. pyloriinfection. Similarly, work on neuronal repair in spinal cord injuries has benefited from the design of nerve conduits to guide nerve regeneration.