Theses Repository

This theses repository is for full-text electronic copies of theses produced by research graduates and postgraduates students from the Dr. Aguila’s Laboratory. It is an Open Access repository, aiming to make the material available to any audience. Titles of all theses, corresponding author, summary, and download link are available in the table below.

2018Lizt Selene Sibila Osorio PandoDeterminación del potencial oncogénico de algunas especies de VPH mediante el análisis in silico de la interacción entre las proteínas E6 y E6APMasterNanoscienceTo date, more than 200 species of papillomaviruses have been reported with the ability to infect epithelial tissue in humans, they are called human papillomavirus (HPV). In addition, there are some species, 12 reported so far, with the ability to infect mucous epithelial tissue, e.g. the anogenital areas, and lead the cell towards a carcinogenic phenotype. While the onset of cellular transformation still remains unclear, the presence of two proteins, E6 and E7, is determinant of HPV carcinogenic potential. E6 protein can interact with a cellular protein called E6AP, which leads to a conformational change in E6 that allows the hijacking and degradation of the p53 protein; consequently, the cell cannot enter apoptosis. Most of the investigations on the function of E6 are carried out in vitro and in vivo, which increases, by far, the cost and time to obtain results. Nowadays, computational simulations or in silico methods offer an attractive alternative for faster and cheaper screening of interacting proteins than in vitro tests. Recently, a research group reported the crystallographic structure of the E6-E6AP complex, opening a new alternative to study molecular interactions between these regulatory proteins. The aim of this work is to study, by in silico methods, the interaction capacity of the E6 protein, from both oncogenic or non-HPV species and the E6AP protein to determine if there is a correlation between the interaction energy of each E6/E6AP complex and the carcinogenic capacity of the virus. To achieve this goal, structural models of E6 proteins were obtained by threading modeling of 24 types of HPV types and the interaction motif of the E6AP (LxxLL). End-point free energy calculations were performed, the calculation of the interaction-free energy was performed based on molecular dynamics simulations and the MM / GBSA and MM / PBSA methods included in the Amber16 program package. The results indicated that overall free energy of interaction between the E6 protein and the motif LxxLL from low risk HPV are very similar to the values obtained for some types of high risk, this result was obtained with both methods of calculation (MM / GBSA and MM / PBSA). Our results indicate that the interaction capacity between E6 proteins and the LxxLL motif is not determinant in the carcinogenic potential of HPV, at least in the types corresponding to the alpha species and under the experimental conditions developed.
2018Gloria Carbajal MartínezDiseño teórico de un árbol solarMasterNanoscienceResearch in photovoltaic solar energy is still under development, looking for new methods to take
advantage of the largest amount of solar energy available. Therefore, the design of solar panels is of vital
importance. The solar tree is an innovative design that has been built for decorative purposes and to
reduce the area needed for installation. However, spiral filotaxis serves as an inspiration to design solar
trees that imitate natural trees and allow for the greater generation of electrical power. In view of this, in
this work, 15 different types of spiral filotaxis were evaluated in 2 different photovoltaic arrays (tree and
Fibonacci tree). These arrangements evaluated with the type of filotaxis 12 allowed to generate more than
10 times of the electrical power that a conventional photovoltaic array (reference), with an inclination
equal to the latitude of Ensenada and oriented to the South. In addition, it was observed that the
photovoltaic array Fibonacci tree generates more electrical power than the tree photovoltaic array. The
above indicates that solar trees are good designs to be implemented to generate more electrical energy.
2018Brianda Paola López SantiniEstudio in silico de la interacción entre el aptámero anti-MUC1 y el epítope de la Mucina 1 López-Santini 2018 (147 downloads) MasterNanoscienceThe rapid expansion of new technologies for targeted cancer therapies has increased the need to develop highly specific agents capable of binding to biologically active molecules or receptors that are expressed abnormally in cancer cells or tissues. Among of the most promising drug delivery strategies for cancer therapy applications are aptamer-mediated nano-vehicles. Aptamers are single stranded DNA or RNA oligonucleotides that fold into unique three-dimensional structures capable of recognizing molecules, such as proteins, phospholipids, sugars or nucleic acids with high affinity and selectivity. In comparison with other binding agents, such as antibodies, they have distinct advantages: their synthesis is easy and inexpensive, they show a low immunogenic and antigenic potential, and they allow a great variety of chemical modifications. Among the best identified ssDNA aptamers we find the anti-MUC1 aptamer which targets the highly repeated epitopes in the extracellular region of the transmembrane glycoprotein Mucin 1, which is mutated and over expressed up to 10-fold in a high number of carcinomas. The aim of this work was to enhance the binding affinity between the anti-MUC1 aptamer and the MUC-1 epitope by mutation scanning in the wild-type aptamer structure. A total of 17 mutations were constructed and simulated by Molecular Dynamics (MD) along 100 ns. Hydrogen bond monitoring and MM/GBSA calculations from selected binding events indicated that three of the mutated aptamers, 11T>1MP, 12T>U and 11T>PSU/12T>U, had better binding abilities than the wild-type aptamer. All three mutations showed a groove formation that structurally favors the aptamer-epitope interaction; an increase in hydrogen bonding count and higher electrostatic interactions that resulted in an overall better free binding energy.
2017Victor Hugo Vargas BermúdezEstudio in silico del genoma del virus de la hepatitis C para buscar su interrupción viral mediante la identificación de fármacos candidatos Vargas-2017 (153 downloads) MasterScience of the LifeHepatitis C virus (HCV) polymerase NS5B has become the main target for the search of potential drugs that can interfere with its activity and inhibit its infection cycle. The objective of the present work is to develop a bioinformatic pipeline for the identification and screening of different lead compounds that could inhibit the activity of the NS5B polymerase. The experimental design consisted of the following steps: the comparison of different protein sequences in search of conserved amino acids in their catalytic site; the analysis of docking assays with different lead compound libraries against NS5B; and the molecular simulation of distinct complexes with candidate ligands. The execution of the different assays herein mentioned, resulted in the discovery of four ligands that demonstrated to interfere equally or even better with protein activity than both sofosbuvir and cannabidiol compounds; two compounds with proven inhibitory effects on NS5B polymerase. Furthermore, these results pave the way to continue research oriented to drug design and in vitro assays with the molecules identified in this study.
2017Joel Ricci LópezEstudio in silico de la proteína E6 del virus del papiloma humano para identificar potenciales fármacos antivirales Ricci 2017 (194 downloads) MasterScience of the LifeHuman papillomavirus (HPV) is one of the most common sexually transmitted infections, and
some HPV strains have been identified as the etiologic agent of some types of cancer. Currently,
there are vaccines capable of preventing infection by these viruses. However, for people that have
already been infected, it is still necessary a drug-based treatment againts the infection and its
oncogenic effects. The oncoprotein E6 is one of the most studied therapeutic targets of HPV, it has
been identified as a key factor in cell immortalization and tumor progression in HPV-positive cells.
E6 is able to promote the degradation of p53, a tumor suppression protein, through the interaction
with the cellular ubiquitin ligase, E6AP. Therefore, preventing E6-E6AP docking is one of the main
strategies to inhibit the viability and proliferation of infected cells.
The present study proposes an in silico methodology focused on the discovery of inhibitors of
the E6-E6AP interaction. To achive this goal, we started with the crystallographic structure of the
E6 HPV-16 protein docked to the LxxLL motif of E6AP, and with 34,804 molecules from the ZINC15
database obtained by their structural similarity with 26 compounds, whose anti-HPV activity has
been previously evaluated. Therefore, a process known as Virtual Screening was performed by
predicting the ADMETox properties of the molecules and preforming docking simulations with the
E6 protein. Then, it was possible to find candidate compounds with favorable pharmacokinetic characteristics
and capable to dock with E6. Finally, four of these compounds were selected, and their
stability in the E6 docked complex and their effect in the inhibition of the E6-E6AP interaction were
corroborated by Molecular Dynamics Simulation. Therefore, this methodology and the identified
molecules represent a new starting point in the development of anti-HPV drugs.
2017Erick Guerrero GonzalezEstudio electroquímico de lacasa de Coriolopsis gallica inmovilizada en nanotubos de carbono modificados con nanopartículas de renio para la detección de compuestos fenólicosEngineeringBioengineering
2017Límbano Aguilar LópezSíntesis de nanopartículas de cobre mediante la utilización del extracto de Egregia sp. para aplicaciones agroalimentariasEngineeringAgrobiotechnologyNanotechnology is a very important and extensive area of research that allows us to manipulate matter on a gauge scale that can demonstrate completely new phenomena and properties, causing scientists to use nanotechnology to create new devices, materials and novel systems that contribute to society current.
Copper nanoparticles have attracted increasing interest, in particular, because of their potential use in catalysis, photovoltaics, energy applications, metallic inks and agricultural area. Copper (Cu) has the advantages of lower cost and greater abundance relative to common catalytic materials, such as platinum or gold. Cu is relatively non-toxic to mammals but is toxic to many microorganisms, and this offers new perspectives for antimicrobial control. This work describes the eco-friendly synthesis of copper nanoparticles from copper sulfate pentahydrate (CuSO4x5H2O) in concentrations of 5, 10,20,30 and 40mM, with different pHs ranging from 6, 8, 10 and 12, and at room temperature, 40, 60 and 80 ° C, and at 100% of extract concentrations. In this methodology, a natural extract obtained from marine algae (Egregia sp and Macrocystis piryfera) was used as a reducing agent, which facilitated the formation of the nanoparticles without residues of toxic contaminants. The nanoparticles were characterized using UV-vis spectroscopy where absorption was determined in the range of 630 to 670 nm, which corresponds to the surface plasmon resonance of the copper nanoparticles. Also, the transmission electron microscopy technique was used to determine the size and shape of the synthesized copper nanoparticles, obtaining an average value of 20 nm.
2017Rafael Betanzos San JuanEfecto de las nanopartículas de cobre sobre la vida de anaquel de Carica papayaEngineeringAgrobiotechnology
2016Enrique Argenis LópezInmovilización de lacasa en nanopartículas magnéticas con fines ambientales, Licenciatura en NanotecnologíaBachelorNanotechnology
2015Patricia Concepción García SuárezEstudio de citotoxicidad y genotoxicidad de productos de reacción de diclorofeno catalizados por lacasa de Coriolopsis gallica en linfocitos humanos García-Suárez 2015 (135 downloads) MasterBionanotecnologíaRestoration of soils and effluents polluting is a problem that has existed along with the environment and the population damage reports from the use of such materials. These pollutants vary polycyclic aromatic compounds, phenols, organochlorine and organophosphates which have several applications in agronomy, industrial and domestic sectors and the property to remain in the environment for long periods of time.
This study was used as a model for the organochlorine dichlorophen, by having a wide range of characteristics of an organic compound, as mentioned in the previous point. In this project, we expose the pesticide before and after of the treatment of immobilized laccase reactor system on human peripheral lymphocytes as a marker of cytotoxic and genotoxic damage on the environmental concentrations by 24 and 48 hours of exposition and hypothesizing that the treatment will be less or non-dangerous after its enzymatic transformation.
The results show decreased cell necrosis (35 %) and a 30% of recovery from cell apoptosis in the transformed pesticide compared with the unmodified compound. The genetic damage it is still a deal, but it is minimized up to 40% in the laccase transformation system.
2014Paulina Tafoya RomoEstudio químico‐computacional de las rutas de transferencia de electrones en hidrogenasa [Ni‐Fe] de Salmonella TyphimuriumEngineeringBioengineering
2014Darío Jaczael Cruz RíosDiseño de un biorreactor multienzimático para la oxidación de colorantes tipo azo, Ingeniería en NanotecnologíaEngineeringNanotechnology