Anabel Torrente

Immune response to gut microbiota in mouse lupus model – Lorena Albaladejo Maricó

7 May, 2022 por Anabel Torrente Leave a Comment

Systemic lupus erythematosus (SLE) is an immune disease in which the immune system mistakenly attacks and damages its own tissues and organs by producing antibodies against them (auto-antibodies). In recent years, several studies have shown that the microorganisms that live in our gut, known as microbiota, play an important role in the development of the disease, possibly due to the inflammation of the gut reported in patients with lupus.
In our group we observed gut inflammation in a mouse model of lupus. It is thought that gut inflammation leads to an increase in intestinal permeability, which would enable gut bacteria to enter the system inducing an immune response that could fuel the inflammation.
Our objective was to determine both the general immune response that takes place in the organism and the gut-associated reaction against the microbiota and/or organs.
To accomplish our goal, we measured the levels of antibodies in blood serum and feces. We also characterized the ability of the serum antibodies to react against microbiota. In future research, the bacteria that get through the intestinal barrier and induce an immune response will be identified.

Keywords: Lupus; antibody; microbiota; gut.

Directed by: Marta Alarcón-Riquelme

Designing new drugs for the treatment of cancer – Laura Erviti Marticorena

7 May, 2022 por Anabel Torrente Leave a Comment

CD44 is a protein that is found on the surface of human cells. It interacts with another protein, hyaluronic acid (HA), causing normal cells to become tumour cells, so enabling tumour development, metastasis and resistance to drug treatment. HA-CD44 interaction is therefore an interesting pharmacological target in cancer therapy.
The main objective of this project is the design, synthesis, and biological evaluation of inhibitors of HA-CD44 interaction, known as derivatives of 1,2,3,4-tetrahydroisoquinoline (THIQ). These molecules act as antitumor agents because they bind to CD44 in a place close to where HA binds, thus inhibiting HA-CD44 interaction. To this end, in this project we study the influence of small variations in the structure of 1,2,3,4-tetrahydroisoquinoline on the inhibition of the HA-CD44 interaction.

Keywords: cancer; inhibitors; hyaluronic acid; CD44, isoquinoline.

Directed by: Ana Conejo García

Battle in the microscopic world: bacteria vs. phages – Daniel Cabrerizo Aguado

7 May, 2022 por Anabel Torrente Leave a Comment

Bacteria, like all living beings, defend themselves against infectious agents, in this case mainly viruses known as “phages”. The mechanisms are extremely diverse and vary from one bacterium to another. Many are not yet fully understood. Recent research showed that many of these systems involve proteins called “Reverse Transcriptases” (RTs). RTs are enzymes that manufacture DNA (where the genetic material is stored), using RNA, an intermediary between DNA and protein, as a template. By the end of 2021, more than 30 bacterial defence systems associated with these RTs had been described. In this project we focused on one of these systems, known as UG17. This system is found in bacteria of the genus Salmonella and Escherichia, among others, and is characterized by the fact that the RT is associated with another protein called SLATT, which is predicted to form pores in the membrane. Although their role in the defence mechanism is still unknown, we demonstrated that the protection of bacteria against infection by some phages requires the participation of both RT and SLATT.

Keywords: Defence systems; UG17; Reverse transcriptase; SLATT

Directed by: Francisco Martínez-Abarca Pastor

Combatting bacteria with very small molecules of silver-DNA – Carmen López Chamorro

7 May, 2022 por Anabel Torrente Leave a Comment

One of the greatest challenges in pharmaceuticals research today is the increase in antibiotic resistance, i.e. the ability of microorganisms to survive in the presence of antibiotics.
This Master’s thesis focuses on developing new drugs with innovative mechanisms using AgI (silver) ions, which can potentially prevent the growth of bacteria (antibacterial activity) and fungi (antifungal activity). DNA molecules (with a double-stranded structure) are used to transport these ions thanks to their high selectivity and versatility in terms of size, shape and sequence. To do this, chemical molecules (nucleobases) that are part of DNA (called guanine and adenine) are replaced by similar molecules (7-deazaguanine and 7-deazaadenine). These deaza-DNA molecules can transport the AgI ions inside the double-stranded DNA. In this way, customized deaza-DNA structures can be formed with base pairs mediated by AgI that can be studied by cell assays. Using this method, we can endow DNA molecules with new antibacterial properties present in the AgI without modifying their geometry. This provides a new way of studying drugs that can help avoid antibacterial resistance.

Keywords: DNA; deaza-DNA; AgI ions; nanostructures.

Directed by: Miguel Ángel Galindo Cuesta

Desing of nanoparticles with potential application in anti-tumour therapy – Ana Medina Moreno

7 May, 2022 por Anabel Torrente Leave a Comment

Nanotechnology is an increasingly important field today due to its wide variety of applications in many areas, including Medicine. One of its most recent applications is in anti-tumour therapy, with drugs that act on specific tissues. Nanoparticles are transport systems for therapeutic agents which aim to increase the efficacy of the drug and its tolerance in the human body. These agents also seek to minimize toxic effects, improving the way in which the drug binds to selected tissues, and its affinity for tumour tissues, thus avoiding the adverse effects produced by conventional chemotherapy.
In this research, nanoparticles of poly(ε-caprolactone), a very stable material compatible with the human body, were formulated. Their characteristics were assessed and several tests were carried out. They were coated with another polymer, chitosan, which also provides all the above advantages, in that it is highly selective for cancerous tissues due to the fact that it decays in their acidic environment and could be a very good alternative in anti-tumour therapy.

Keywords: Anti-tumour therapy, nanotechnology, nanoparticles, poly(ε-caprolactone), chitosan.

Directed by: José Luis Arias Mediano