e-Repositori UPF :: Grau en Biologia Humana. Treballs de fi de grau

Recent Submissions

Mechanism of Action of an SGLT2 Inhibitor in Renal Cellular Damage
(2025) Vecino Feliz, Sofia
Diabetic kidney disease (DKD) is now the principal cause of chronic kidney disease, leading to end-stage kidney disease worldwide, increasing morbidity and mortality and resulting in elevated costs for public health systems. Its multifactorial etiology encompasses metabolic, hemodynamic, inflammatory, and fibrotic mechanisms, with chronic hyperglycemia as the primary driver of renal injury. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have emerged as promising agents in the management of diabetic nephropathy, not only improving glycemic control but also exerting protective effects through modulation of glomerular hemodynamics, reduction of cardiovascular (CV) risk, and anti-inflammatory and antifibrotic actions. However, the precise biological mechanism underlying these benefits remains incompletely understood. This project aims to elucidate the physiological pathways modulated by SGLT2 inhibitors in order to clarify the molecular basis of SGLT2 inhibitor-mediated kidney protection and provide insights for the development of targeted therapeutic strategies in diabetic nephropathy.
Early biomarkers through transcriptomic profiling in young COPD patients: insights into sex-specific differences
(2025) Ramos Osorio, Nicole Ximena
Chronic Obstructive Pulmonary Disease (COPD) is a frequently underdiagnosed (by over 70%) disease due to its heterogeneity and the current diagnostic criteria, which make it challenging to diagnose in the early stages. This study aims to identify transcriptomic biomarkers in blood samples to facilitate early diagnosis and improve our understanding of the biological pathways involved, paying particular attention to sex differences. Whole blood RNA samples from 37 patients and 35 matched controls (14 and 18 females, respectively) were analysed. Differential expression analyses were performed for COPD patients compared to controls, both globally and stratified by sex. An empirical Bayes approach was used to adjust for sex and age. Predictive models were built using Support Vector Machine and Random Forest algorithms with K-best AI feature selection. A total of 511, 569, and 378 genes were differentially expressed in the global, female, and male analyses, respectively (p < 0.05), with 11 genes being common to all comparisons. Diagnostic models demonstrated high performance, particularly in sex-specific models based on AI selection (accuracy ≥ 95%; MCC ≥ 0.87), which outperformed models based on shared genes. The selected transcripts were related to immune response, oxidative stress, energy metabolism and ciliary function, some of which were modulated in a sex-specific manner. Our results suggest that the pathogenic mechanisms of COPD may differ between men and women. This highlights the importance of considering sex as a relevant biological factor in COPD research. They provide new insights into the early pathobiology of COPD and contribute to the move towards personalised medicine.
Development of computational sequence analysis for the characterization of Hepatitis E in Catalonia
(2024) Juliachs Torroella, Gisela
Hepatitis E virus (HEV) is a zoonotic virus that causes acute hepatitis with increasing incidence in humans in Europe which is mainly transmitted by the consumption of undercooked pig meat. Zoonotic genotypes HEV-3 and HEV-4 are zoonotic and predominant in Europe. The use of animal collective environmental samples (slurry from farms and wastewater from slaughterhouses and wastewater treatment plants (WWTP)) to study the circulation of HEV genotypes in Catalonia. Samples have been concentrated and analyzed by (RT)qPCR and n(RT)PCR. HEV genotypes have been subtyped using amplicon-deep sequencing (ADS) with minION by an optimized bioinformatic pipeline. The impact of several parameters in the bioinformatic pipeline such as trimming, clustering, and subsampling have been evaluated. A quality score of 7 with clustering the sequences at 90% of homology were selected for the bioinformatic pipeline. In total, 14 HEV subtypes were detected in the study. HEV-3f and HEV-3e are predominant in environmental samples near areas impacted by the pig industry. HEV-3c is the majoritarian genotype in WWTP with low contact to the branch sector. Samples had a minoritarian presence of HEV-3oni. These results are part of a pilot study which combines ADS and computational analysis to elucidate the HEV genotypes and their zoonotic potential.
G2019S mutation in the LRRK2 gene increases endosomal recruitment in iPSC-derived microglia
(2024) Homet i Pagès, Marcel
Parkinson’s disease (PD) is an uncurable neurodegenerative disorder associated with progressive death of dopaminergic neurons and formation of Lewy’s Bodies, containing α-synuclein. Growing evidence suggests that PD progresses in a non-cell-autonomous manner, involving among others microglia, central nervous system macrophages. Genetic variation around the LRRK2 gene is associated with both familial and sporadic PD. In particular, the G2019S is the most common monogenic PD mutation. Although the cellular role of LRRK2 is only partially understood, an implication of the protein in the regulation of vesicle trafficking in the endolysosomal system has been highlighted. With this project we aim to elucidate LRRK2 role in the microglial endolysosomal system and whether an alteration of the system may lead to a rerouting of vesicle trafficking. Employing induced pluripotent stem cells, we generated microglia from a LRRK2 PD patient and its isogenic gene-corrected counterpart. Our findings highlight an impaired autophagy in LRRK2 PD iPSC-derived microglia and an increased recruitment of endosomes towards the lysosomes. In addition, we observed that in LRRK2 PD microglia a fraction of LE is addressed to the plasma membrane, probably for secretion. These results collectively suggest that G2019S mutation in LRRK2 gene in microglia may contribute to PD pathogenesis by impairing lysosomal degradation and increasing endosomal trafficking that may affect neuron survival.
Toolkit development for identification of GABAergic neuronal subpopulation and conditional control of ectopic gene expression
(2024) Sanmartín Cerrato, Victoria
The hindbrain is the most posterior part of the vertebrate brain. This evolutionarily ancient region contains distinct progenitor cell populations that will give rise to different neuronal identities. Neurogenesis starts with the expression of proneural genes, which commit cells to the neuronal lineage and activates the differentiation pathway. However, the mechanism of how proneural genes can influence neuronal differentiation remains unclear. In this study, we developed two tools to investigate how proneural genes are regulated to trigger neuronal differentiation, focusing on the zebrafish hindbrain. First, since we are interested in GABAergic neurons, we aimed to investigate the potential of homeodomain transcription factors as putative markers by gene expression. Our findings indicate that gata3 and dbx1a exhibit specific expression patterns in mediodorsal regions at 76 hours postfertilization. Second, we designed a system to enable the ectopic gene expression in specific neuronal progenitors, allowing for conditional control of gene expression together with cell tracing. Our results indicate the correct obtention of two out of three plasmids needed. To sum up, we generated useful tools that will contribute to the understanding how proneural genes regulate differentiation.
Investigating the role of fgf13 in the statoacoustic ganglion morphogenesis in Danio rerio
(2024) Barbero Durán, Nuria Mei
The statoacoustic ganglion (SAG) is the inner ear sensory ganglion, composed of bipolar neurons that send projections to the hair cells of the inner ear and the hindbrain. Fibroblast growth factor 13 (fgf13), a microtubule-stabilising protein, involved in axon branching and leading processes, is highly expressed in developing sensory neurons of the head. This research project examines the critical role of fgf13 paralogs (fgf13a and fgf13b) in early neuronal progenitor migration and axonogenesis in the zebrafish SAG, by evaluating morphological and axon formation variations in a double knockout (KO) stable line. Confocal imaging of Tg(neurod1:eGFP) / fgf13a/b KO zebrafish SAGs revealed no major morphological differences between mutants and control embryos, however previous results on F0 injected embryos showed SAG development impairment. Posteriorly, a quantitative real-time polymerase chain reaction (qRT-PCR) analysis of fgf12a/b mRNA expression showed no differences in the fgf12 mRNA expression, suggesting fgf12 is not responsible for the compensation on the KO line embryos. Due to compensation or other mechanisms, the study could not decipher the role due to limited fish breeding and time preparation of new experimental procedures. However, elucidation of the role of fgf13 could unravel the participation in understanding auditory disorders.
Technical and clinical validation of glial reactivity biomarkers sTREM2 and YKL-40 in Alzheimer’s disease
(2024) Sambola Lloveras, Berta
Glial reactivity plays an important role in the pathogenesis of Alzheimer’s disease (AD). Biomarkers associated with this process have the potential for understanding AD pathogenesis and facilitating the development of novel therapeutic strategies. Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) and YKL-40, also known as chitinase 3-like protein 1 (CHI3L1), are involved in the modulation of these glial responses. Our study aimed to conduct both technical and clinical validation of an in-house Meso Scale Discovey (MSD) assay and a commercial enzyme-linked immunosorbent assay (ELISA) for quantifying these biomarkers in cerebrospinal fluid (CSF) of AD patients. Technical validation included spike recovery, parallelism and precision tests. Clinical validation involved investigating the biomarker correlations with demographic factors within the cohort and the differences between biologically diagnosed AD and non-AD patients. Both assays showed high accuracy, robustness, and consistency in measuring CSF sTREM2 and YKL-40. Both biomarkers increased with age and CSF YKL40 was higher in patients with biological defined AD. Additionally, significant correlations were observed between CSF sTREM2, YKL-40, and the core CSF biomarkers Aβ40, Aβ42, and pTau181. No significant associations were found between CSF sTREM2, YKL-40, sex, APOE ε4 profile and MMSE scores.
Impact of the COVID-19 pandemic on sickness absence rates in healthcare workers: a retrospective cohort study in a Spanish hospital
(2023) López Millán, Brais
The COVID-19 pandemic has affected the working conditions and social demands of healthcare workers (HCWs). This study focuses on analyzing sickness absence rates among HCWs in a Spanish hospital from 2018 to 2022, considering sociodemographic and occupational variables. Logistic regression models have allowed to assess the correlation between work variables and the probability of having a sickness absence each year. The results show that sickness absence rates increased significantly in late 2021 and remained elevated throughout 2022. Despite all workers suffering significant increases in incidence rates, female HCWs consistently had higher rates compared to males. Occupational category was found to be a key determinant, with nurse aides experiencing the highest rates in post-pandemic years. Additionally, nurses and nurse aides had greater odds of having sickness absences compared to doctors. Having worked in critical care or the emergency room during the pandemic was also associated with higher incidence rates. Overall, the findings highlight the impact of working conditions on HCWs' health and the need to address the underlying systemic issues in healthcare systems. Understanding the occupational determinants of sickness absence can help in developing strategies to improve the well-being of HCWs and ensure a healthy and stable workforce.
Socioeconomic determinants of early neurodevelopment
(2023) Vallet Casadevall, Julieta
Socioeconomic status (SES) can be determinant for human health. Through different mechanisms, a person’s educational level, occupational status and income can define their physical and mental well-being. Considering that in the first years of life and even before being born, infants are especially vulnerable to their environment, we analyze whether social and economic factors may have an effect on early neurological development. Using data from the BiSC cohort (women recruited in three major hospitals in Barcelona) and multivariate regression models, we determine the relationship between maternal educational level, financial management, employment status and health insurance, with the neurodevelopment of their offspring assessed through the Developmental Profile 3 (DP-3) questionnaire. Possible confounding variables, such as sex of the child, weight at birth or maternal age, amongst others, were controlled for statistically. Results indicate that there is no effect of health insurance in early development. Higher time-demanding maternal employment has been found to cluster with lower scores in different dimensions of the DP-3 test. Outcome regarding the influence of maternal education and income is controversial. These effects are discussed, emphasizing the potential role of parental bias while reporting their children’s skills.
Assessment of the optical genome mapping technique in splenic marginal zone lymphoma: a comparison with cytogenomic data
(2023) Teixidó Mulet, Mar
Splenic marginal zone lymphoma (SMZL) is a genetically heterogeneous entity, entailing the need for further genetic characterization to deepen the knowledge of its prognosis and optimize its diagnosis. Karyotype and FISH assays remain the standard of care (SOC) for hematologic malignancies analysis, techniques that often fail to unveil the genetic complexity of the tumor cells. Optical genome mapping (OGM) is a novel high-resolution non-sequencing technique, recently proposed as a promising diagnostic alternative. Herein, we assess the OGM technique in the genetic characterization of 14 SMZL patients, comparing it to SOC cytogenomic results. OGM uncovered 24 cytogenetically cryptic variants, providing finer alteration breakpoints, unveiling the origin of derivative chromosomes seen in the karyotype, and, thanks to its genelevel resolution, included involved genes relevant to SMZL. The OGM results showed a 70% concordance with SOC techniques, lower than reported in recently published literature in acute leukemias, attributable to telomere and centromere involvement of alterations or a low variant allele frequency (VAF), current limitations which would need further addressing. These results demonstrate the potential advantages of OGM for mature B-cell neoplasms characterization, encouraging the implementation of the OGM technology in the clinical setting alongside traditional cytogenetic techniques.
Optimization of sTREM2 ELISA to understand the role of microglia in Alzheimer's disease
(2023) Miret Milian, Maria
Triggering receptor expressed on myeloid cells 2 (TREM2), a microglial receptor, plays a crucial role in the innate immune response in Alzheimer's disease (AD), aiding in the clearance of amyloid beta plaques and preventing Tau propagation. As a result of cleavage, soluble TREM2 (sTREM2) can be detected in human cerebrospinal fluid (CSF) and plasma across the AD continuum, serving as a biomarker of microglial activity. This study aimed to optimize a Meso Scale Discovery (MSD) enzyme-linked immunosorbent assay (ELISA) for the quantification of sTREM2 in biofluids. Validation parameters considered for optimization included signal-to-noise (S/N) ratio, background noise and coefficient of variation (CV%). Optimal capture and detection antibodies concentrations were determined to be 15.63 ng/ml and 0.125 μg/ml, respectively, resulting in improved assay performance. Despite higher background noise, storing MSD reagents at 4ºC and the use of MSD Small Spot coated-streptavidin plates improved the S/N ratio. Finally, a concentration of 0.0625 μg/ml of secondary antibody rendered a lower background and higher S/N ratio. These optimizations significantly increased the sensitivity and accuracy of the immunoassay, making it a promising tool for the early detection of pathological alterations linked to AD.
Hindbrain rhombomere centers harbor an heterogenous population of dividing progenitors
(2023) Hernández Martin, Ariadna
During embryonic development, tissue growth and morphogenesis are interconnected processes and their regulation is essential to correctly develop an organism. This regulation involves the controlled production of different cell types and the precise allocation of stem cell capacities at the right time. The embryonic zebrafish hindbrain is a notable example of how the spatial and temporal acquisition of cell diversity is linked to tissue growth, as neurogenesis depends on the position of progenitor cells along the anteroposterior axis. However, the exact coordination mechanisms behind this process are not fully understood. Through a combination of cell lineage and in vivo imaging, we have discovered certain characteristics of the cell population located in the hindbrain rhombomeric centers. By performing clonal analysis, we have investigated the proliferative capacity of this region, providing new insights into the behavior of this cell population. This work shows the spatiotemporal molecular profile of rhombomeric center. Moreover, our findings suggest that rhombomere centers harbor a heterogeneous progenitor population where proliferative capacities get restricted around 48hpf and this territory gets arrested in G1 cell phase of the cell cycle. In conclusion, centers of rhombomeres present characteristics comparable to long lasting progenitors.
De la neurociència a les aules: impacte de les competències socioemocionals en la creativitat i la cognició
(2022) Pocurull Masferrer, Aina
Les emocions tenen un impacte extens i substancial en els processos cognitius, i el seu paper en la cognició i la creativitat és estudiat per diverses línies de recerca, des de l’àmbit educatiu fins al camp de la neurociència. L’objectiu d’aquest estudi és avaluar l’impacte que genera treballar les competències socioemocionals en la cognició i la creativitat dels adolescents. Per aquest motiu, s’ha emprat un disseny quasi experimental on han participat 203 estudiants de secundària de 3 centres educatius de Catalunya; 106 han format part del grup control i 97 de l’experimental. Per dur-ho a terme, ambdós grups han realitzat dos tests: un test de creativitat que analitza la creativitat narrativa, el pensament divergent i el pensament convergent, i un test de cognició, que avalua la memòria de treball. Prèviament, el grup experimental ha fet una dinàmica socioemocional per avaluar l’impacte que les competències socioemocionals treballades han tingut en la creativitat i la cognició. La dinàmica socioemocional no ha mostrat diferències significatives en la memòria de treball, però s’ha evidenciat un impacte significatiu en la creativitat narrativa i el pensament divergent dels estudiants. Aquest estudi suggereix la rellevant importància de treballar les competències socioemocionals a l’aula per potenciar la creativitat.
Study of the mechanism underlying the effect of 5-HT in microglial processes motility
(2022-10-26) del Río i Torné, Carla
Microglia, the brain's resident macrophages, have a distinct ramified morphology orchestrated by repeated cycles of extension and retraction of their long thin processes, allowing them to continuously monitor their environment. Microglia play a role in the homeostasis and functional integrity of the brain parenchyma. Microglia are known to extend their processes in a directional manner in response to tissue damage via activation, by ATP release from damaged sites, of the P2Y12 receptor (P2Y12R) which is expressed by all microglia. Moreover, the laboratory previously reported that the neuromodulator serotonin (5-HT) also has the potential to trigger microglial process outgrowth i.e. “directional motility” toward a focal 5-HT application site. This is allowed sensing of 5-HT by the microglial 5-HT2B receptor (5-HT2BR), which is the main serotonin (5-HT) receptor expressed by microglial cells. Intriguingly, this response to 5-HT also requires microglial P2Y12R and extracellular ATP/ADP, but the mechanism and signaling pathway involved remain elusive. Moreover, it is not known whether all or only a subset of microglia can sense 5-HT. In this work, using the RNA-Scope method, we were able to see the 5-HT2BR expression in different brain regions and notably in a subset of microglial cells. Furthermore, using a fluorescent biosensor for ATP and primary glial cells cultures, we show that 5-HT may trigger the release of ATP by mixed cultures of microglia and astrocytes. Altogether, these findings support the hypothesis that in vivo, 5-HT could have an effect on a large number of microglial cells by activating initially only a few, which in turn would trigger the release of ATP and increase processes motility.
Characterizing cortical bioenergetics in a mouse model of Alzheimer’s disease
(2022-10-18) Ausellé Bosch, Sira
Alzheimer's Disease (AD) currently represents the most common neurodegenerative disease worldwide. The complete underlying mechanisms of its physiopathology are still unknown, but brain bioenergetics and the endocannabinoid system (ECS) have emerged as potential novel therapeutic targets in AD. This project aimed to clarify whether mitochondrial alterations could be linked with the behavioural alterations found in a mouse model of AD treated with cannabinoid drugs, considering sex differences as an important factor. First, we assessed the expression of the oxidative phosphorylation system (OXPHOS) complexes by Western Blot assays in cortex samples from 12-month-old WT and APP/PS1 male and female mice. Despite no significant results were obtained, behavioural correlations indicate an association between conduct and molecular processes. Furthermore, we performed liquid chromatography-mass spectrometry to quantify the most relevant metabolites of the Krebs cycle. Our results suggest a few alterations in APP/PS1 male mice in some metabolites and enzymes that could have a role in AD’s pathology. Overall, this study opens the possibility of a feasible interesting link between bioenergetics, cannabinoids and AD pathology. Even though, further research should be performed to achieve a better knowledge of the disease and explore these new targets to improve early diagnosis and therapeutic approaches.
Aturem la transmissió per mosquits: disseny d’un projecte - a partir de la Guia ABPxODS - pel desenvolupament de les competències clau per a la sostenibilitat
(2022-07-27) Magrinyà Estrada, Joan
Els problemes d’abast mundial actuals exigeixen un canvi urgent en la nostra manera de pensar i actuar. Per aquest motiu, cal entendre l’educació com un instrument essencial per la transformació social cap a la consecució dels Objectius de Desenvolupament Sostenible, descrits per l’ONU a l’Agenda 2030. En aquest context, els sistemes educatius han d’incloure pedagogies innovadores de qualitat que promoguin el desenvolupament de les competències clau per a la sostenibilitat, apoderant als estudiants a esdevenir-ne els promotors del canvi. Últimament, l’aprenentatge basat en projectes està guanyant força com a metodologia capaç de promoure coneixements i habilitats personals en l’alumnat, amb les que respondre a problemàtiques complexes. Així doncs, dins del marc compartit entre ABP i ODS, aquest article presenta el disseny d’un projecte ( Aturem la transmissió per mosquits) elaborat a partir de la Guia ABPxODS, que té com a finalitat impulsar la participació dels estudiants en la generació i divulgació d’estratègies sostenibles per abordar les diferents fites plantejades a l’Agenda 2030, a més de sensibilitzar a la ciutadania local sobre la urgència d’una actuació immediata. Concretament, es focalitza en la problemàtica actual de les malalties transmeses per mosquits arreu del món, per aprofundir en l’ODS 3 - Salut i benestar.
Global prevalence and incidence of Alzheimer’s disease and mild cognitive impairment
(2021) Díaz Guindo, Marta
Alzheimer’s disease (AD) is the most prevalent cause of dementia worldwide. AD is characterized histopathologically by senile plaques composed of amyloid β-peptide (Aβ) and neurofibrillary tangles consisting of aggregated tau protein. AD onset is preceded by mild cognitive impairment (MCI) where it is supposed that oligomers start to damage synapses. In a world with a rising number of people aged 65 and older, MCI and AD have become a public health problem. Therefore, the aim of this review is to collect the current knowledge on MCI and AD epidemiology, highlighting the social and biological factors that produce regional differences in their prevalence. To achieve this goal, we have searched original articles, meta-analysis publications and reviews published since 2010 on epidemiology. As expected, the epidemiological data show divergent values between countries, age and sexes. Factors such as genetic polymorphisms, cardiovascular diseases, diabetes and educational level are changing AD and MCI rates through the last decades. Even though the efforts done to collect population data, further studies need to be performed around the world. Studding the evolution of AD prevalence by ages from normal cognitive status to severe stages of AD will be crucial to foresee economic expenses in the future.
Elucidating the pathophysiological role of the apoptosis inducing factor 1 (AIF1) in Alzheimer's disease: a review of its participation in other pathologies
(2021) Solé Ariza, Aina
Alzheimer’s disease (AD) is the most common cause of age-related dementia, whose progression and development are explained by two well-based hypotheses. The amyloid cascade hypothesis proposes the aggregation of the amyloid ß-peptide (Aß) as the key event that triggers AD, whereas the mitochondrial cascade hypothesis claims that neurodegeneration is caused by oxidative stress and mitochondrial dysfunction. Even so, both hypotheses are not independent since a relationship between them is already known. Many questions about its physiopathology, however, remain unanswered. The present review proposes the possible participation of the apoptosis inducing factor 1 (AIF1) in AD, a highly relevant mitochondrial protein both for cell survival (OXPHOS process) and for cell death (caspase-independent apoptosis). According to the known functions the AIF1 performs in other pathologies, it can be suggested that the Aß accumulation and oxidative stress produces the release of pro-apoptotic AIF1, which contributes to mitochondrial dysfunction and apoptosis in hippocampus neurons. Nevertheless, the dual functionality of AIF1 represents one of the greatest challenges to clearly define the involvement of the protein in AD, so further studies are required in this direction.
Study of the molecular basis of congenital disorders of glycosylation using yeast as a model organism
(2021) Guiu Gonzalez, Neus
Congenital Disorders of Glycosylation (CDG) are a group of inherited human disorders caused by defects on protein glycosylation. Rft1-CDG is a form of CDG caused by mutations in the gene RFT1. Rft1 is a conserved protein essential for the N-linked glycosylation pathway in the ER. The subcellular localization of Rft1 has not been explored experimentally, although it is crucial for Rft1 function and protein glycosylation. The purpose of this research is to characterize the subcellular distribution of Rft1 and to investigate the molecular defects caused by Rft1-CDG mutations using S. Cerevisiae as a model organism. To answer this question, we investigated the colocalization between GFP tagged Rft1 and several mCherry tagged subcellular structures using fluorescence microscopy. We found that wild-type GFP-Rft1 localizes in the Endoplasmic Reticulum (ER), the Golgi Apparatus, endosomes and mitochondria. The Rft1-CDG mutations introduced to the GFP-Rft1 strain were R179E, M446V, I340K, G320D, I340R and R75C. Results show that in Rft1-R179E mutant yeast strain, the localization of Rft1 within the cell remains similar to the wild-type. However, the intensity distribution of the GFP-Rft1 fluorescent signal in mutants Rft1-R179E and Rft1-I340K is altered and the duplication time of these particular mutants and Rft1-G320D mutant is increased. Our results provide, for the first time, observations of the impact of Rft1-CDG mutations that can contribute identifying the molecular basis of human CDG.
Inhibition of TELO2 sensitizes colorectal cancer cells to chemotherapies
(2019) Ortiz Gràcia, Alba
Colorectal cancer is the 2nd most killing cancer around the world. Because treatments generally involve DNA damage, high toxicity and undesirable effects are frequently observed, which lead to treatment suspension. Moreover, several resistances to chemotherapy have been reported. Therefore, the research for new therapeutic approaches has become a major challenge. In this project our aim was to test the therapeutic potential of the protein TELO2 in combination with chemotherapy in colorectal cancer. TELO2 impacts the DNA damage response by affecting the stability of ataxia telangiectasia mutated (ATM) and ataxia telangiectasia and Rad3-related (ATR) proteins. Indeed, the three classically used chemotherapies: oxaliplatin, irinotecan and 5-fluorouracil, are based on DNA damage production. We used a HCT116 derivative cell line with an auxin-inducible degron fused the endogenous TELO2 protein. We found additive effect with oxaliplatin, and synergistic effects with low doses of irinotecan and 5-fluorouracil. These results encourage to keep on researching for alternative approaches to enhace the response-rate to colorectal cancer treatments.

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