Robi Tacutu

Robi Tacutu
Institutul de Biochimie | IB · Bioinformatics and Structural Biochemistry

PhD

About

65
Publications
5,707
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
1,794
Citations
Additional affiliations
September 2016 - present
Institutul de Biochimie
Position
  • Head of Department
November 2011 - May 2016
University of Liverpool
Position
  • PostDoc Position
January 2008 - December 2011

Publications

Publications (65)
Article
EDEM-1, EDEM-2 and EDEM-3 are key players for the quality control of newly synthesized proteins in the endoplasmic reticulum (ER) by accelerating disposal and degradation of misfolded proteins through ER Associated Degradation (ERAD). Although many previous studies reported the role of individual ERAD components especially in cell-based systems, st...
Article
Full-text available
If somatic stem cells would be able to maintain their regenerative capacity over time, this might, to a great extent, resolve rejuvenation issues. Unfortunately, the pool of somatic stem cells is limited, and they undergo cell aging with a consequent loss of functionality. During the last decade, low molecular weight compounds that are able to indu...
Article
Full-text available
Tissue fibrosis is a major driver of pathology in aging and is involved in numerous age-related diseases. The lungs are particularly susceptible to fibrotic pathology which is currently difficult to treat. The mouse bleomycin-induced fibrosis model was developed to investigate lung fibrosis and widely used over the years. However, a systematic anal...
Article
Full-text available
Genetic manipulations can ameliorate the aging process and extend the lifespan of model organisms. The aim of this research was to identify novel genetic interventions that promote both lifespan and healthspan, by combining the effects of multiple longevity-associated gene inactivations in C. elegans. For this, the individual and combined effects o...
Preprint
Full-text available
Dysregulation of intercellular communication is a well-established hallmark of aging. To better understand how this process contributes to the aging phenotype, we built scAgeCom, a comprehensive atlas presenting how cell-type to cell-type interactions vary with age in 23 mouse tissues. We first created an R package, scDiffCom, designed to perform d...
Article
Full-text available
In this paper, we propose a method of learning representation layers with squashing activation functions within a deep artificial neural network which directly addresses the vanishing gradients problem. The proposed solution is derived from solving the maximum likelihood estimator for components of the posterior representation, which are approximat...
Chapter
Traditionally, gerontologists have focused on studying various aspects of aging one at a time. Thanks to recent post-genome technologies, however, this paradigm is shifting and researchers can now focus on more holistic approaches rather than being limited to the study of isolated parts. In this chapter, we review the use of high-throughput technol...
Article
Full-text available
Accumulating metabolomics data is starting to become extremely useful in understanding the ageing process, by providing a snapshot into the metabolic state of tissues and organs, at different ages. Molecular studies of such metabolic variations during “normal” ageing can hence guide lifestyle changes and/or medical interventions aimed at improving...
Article
Full-text available
Interventional studies on genetic modulators of longevity have significantly changed gerontology. While available lifespan data are continually accumulating, further understanding of the aging process is still limited by the poor understanding of epistasis and of the non-linear interactions between multiple longevity-associated genes. Unfortunately...
Chapter
Health and pathologies are multifactorial states characterizing how well biological systems function in a range of conditions and facing various stressors. Depending on how flexible the definition of a state is, systems may have multiple healthy and stable states. However, keeping homeostasis requires parameters dynamically fluctuating within a phy...
Article
One important question in aging research is how differences in genomics and transcriptomics determine the maximum lifespan in various species. Despite recent progress, much is still unclear on the topic, partly due to the lack of samples in nonmodel organisms and due to challenges in direct comparisons of transcriptomes from different species. The...
Preprint
Full-text available
Interventional studies on genetic modulators of longevity have significantly changed gerontology. While available lifespan data is continually accumulating, further understanding of the aging process is still limited by the poor understanding of epistasis and of the non-linear interactions between multiple longevity-associated genes. Unfortunately,...
Article
Full-text available
Background: Cellular senescence, a permanent state of replicative arrest in otherwise proliferating cells, is a hallmark of aging and has been linked to aging-related diseases. Many genes play a role in cellular senescence, yet a comprehensive understanding of its pathways is still lacking. Results: We develop CellAge (http://genomics.senescence...
Article
Full-text available
Leucine-rich-repeats (LRRs) belong to an archaic procaryal protein architecture that is widely involved in protein–protein interactions. In eukaryotes, LRR domains developed into key recognition modules in many innate immune receptor classes. Due to the high sequence variability imposed by recognition specificity, precise repeat delineation is ofte...
Preprint
Full-text available
One important question in aging research is how differences in genomics and transcriptomics determine maximum lifespan in various species. Despite recent progress, much is still unclear on the topic, partly due to the lack of samples in non-model organisms and due to challenges in direct comparisons of transcriptomes from different species. The nov...
Preprint
Full-text available
Cellular senescence, a permanent state of replicative arrest in otherwise proliferating cells, is a hallmark of ageing and has been linked to ageing-related diseases like cancer. Senescent cells have been shown to accumulate in tissues of aged organisms which in turn can lead to chronic inflammation. Many genes have been associated with cell senesc...
Data
Table S1 List of species used for orthology analysis.
Data
Fig. S1 Percentage of Interactome LAG orthologs from the four model species. Fig. S2 Percentage of LAG orthologs from the four model species after exclusion of proteins from enriched categories. Fig. S3 GO Slim summary and enrichment analysis. Fig. S4 Conservation index (CI) compared to concordancy of longevity effects. Fig. S5 Method similarit...
Data
Table S2 Enrichment of KEGG and GOCC pathways in Longevity Associated Genes (LAGs) from different species.
Data
Table S6 Enrichment analysis of lifespan extending Longevity‐associated genes (LAGs) under different criteria and backgrounds.
Data
Table S3 List of proteins under different evolutionary conservation criteria.
Data
Table S5 Enrichment analysis of lifespan decreasing Longevity‐associated genes (LAGs) under different criteria and backgrounds.
Data
Table S7 List of LAGs that are listed as stress response genes under the GO classification system.
Data
Table S4 Enrichment analysis of Longevity‐associated genes (LAGs) under different criteria and backgrounds.
Data
Table S8 Pairwise concordance of LAG manipulation.
Article
Full-text available
In spite of a growing body of research and data, human ageing remains a poorly understood process. Over 10 years ago we developed the Human Ageing Genomic Resources (HAGR), a collection of databases and tools for studying the biology and genetics of ageing. Here, we present HAGR's main functionalities, highlighting new additions and improvements. H...
Preprint
Full-text available
In spite of a growing body of research and data, human ageing remains a poorly understood process. To facilitate studies of ageing, over 10 years ago we developed the Human Ageing Genomic Resources (HAGR), which are now the leading online resource for biogerontologists. In this update, we present HAGR’s main functionalities, including new additions...
Article
Full-text available
Hundreds of genes, when manipulated, affect the lifespan of model organisms (yeast, worm, fruit fly, and mouse) and thus can be defined as longevity-associated genes (LAGs). A major challenge is to determine whether these LAGs are model-specific or may play a universal role as longevity regulators across diverse taxa. A wide-scale comparative analy...
Preprint
Full-text available
Hundreds of genes have been identified as being involved in the control of lifespan in the four common model organisms (yeast, worm, fruit fly and mouse). A major challenge is to determine if longevity-associated genes (LAGs) are model-specific or may play a universal role as longevity regulators across diverse taxa. A wide-scale comparative analys...
Chapter
Traditionally, gerontologists have focused on studying various aspects of aging one at a time. Thanks to recent post-genome technologies, however, this paradigm is shifting and researchers can now focus on more holistic approaches rather than being limited to the study of isolated parts. In this chapter, we review the use of high-throughput technol...
Article
Full-text available
In model organisms, over 2,000 genes have been shown to modulate aging, the collection of which we call the “gerontome”. Although some individual aging-related genes have been the subject of intense scrutiny, their analysis as a whole has been limited. In particular, the genetic interaction of aging and age-related pathologies remains a subject of...
Data
Table S2 Full list of results from the Connectivity Map. Specificity score gives an estimate of how unique the similarities of the drugs’ expression profile to the query expression profile are.
Data
Fig. S1 Percentage survival of wild‐type (N2) or eat‐2 mutant worms alone or treated with geldanamycin. Fig. S2 Percentage survival of wild‐type (N2) or eat‐2 mutant worms alone or treated with a regular or double dose of trichostatin A (TSA). Fig. S3 Percentage survival of wild‐type (N2) or eat‐2 mutant worms alone or treated with a regular or d...
Data
Table S1 Human genes used to query the Connectivity Map and their relative change in the CR transcriptional profile used. Table S3 The variation seen in lifespan compared to controls of each treatment.
Data
Table S4 Full list of differentially expressed genes.
Data
Table S5 Functional enrichment for genes differentially expressed under various treatments.
Data
Table S7 Tabulated lifespan data for Figures 1, 2, S1, S2 and S3.
Data
Table S6 List of differentially expressed longevity‐associated genes.
Article
Full-text available
Background Caloric restriction (CR) can increase longevity in rodents and improve memory function in humans. α-Lipoic acid (LA) has been shown to improve memory function in rats, but not longevity. While studies have looked at survival in rodents after switching from one diet to another, the underlying mechanisms of the beneficial effects of CR and...
Article
Full-text available
Caloric restriction (CR), a reduction in calorie intake without malnutrition, retards aging in several animal models from worms to mammals. Developing CR mimetics, compounds that reproduce the longevity benefits of CR without its side effects, is of widespread interest. Here, we employed the Connectivity Map to identify drugs with overlapping gene...
Article
Full-text available
Mitochondria are the only organelles in the animal cells that have their own genome. Due to a key role in energy production, generation of damaging factors (ROS, heat), and apoptosis, mitochondria and mtDNA in particular have long been considered one of the major players in the mechanisms of aging, longevity and age-related diseases. The rapidly in...
Article
Full-text available
Wound healing is an inherent feature of any multicellular organism and recent years have brought about a huge amount of data regarding regular and abnormal tissue repair. Despite the accumulated knowledge, modulation of wound healing is still a major biomedical challenge, especially in advanced ages. In order to collect and systematically organize...
Article
Full-text available
Multiple studies characterizing the human ageing phenotype have been conducted for decades. However, there is no centralized resource in which data on multiple age-related changes are collated. Currently, researchers must consult several sources, including primary publications, in order to obtain age-related data at various levels. To address this...
Article
Understanding the genetic basis of human longevity remains a challenge but could lead to life-extending interventions and better treatments for age-related diseases. Toward this end we developed the LongevityMap (http://genomics.senescence.info/longevity/), the first database of genes, loci, and variants studied in the context of human longevity an...
Article
Full-text available
The Human Ageing Genomic Resources (HAGR, http://genomics.senescence.info) is a freely available online collection of research databases and tools for the biology and genetics of ageing. HAGR features now several databases with high-quality manually curated data: (i) GenAge, a database of genes associated with ageing in humans and model organisms;...
Article
Full-text available
Intricate and interconnected pathways modulate longevity, but screens to identify the components of these pathways have not been saturating. Because biological processes are often executed by protein complexes and fine-tuned by regulatory factors, the first-order protein-protein interactors of known longevity genes are likely to participate in the...
Data
First-order interactors of LAGs in the WLN (without shared genes with HLN) assayed in C. elegans . (DOCX)
Data
Shared first-order interactors of LAGs found in WLN and HLN assayed in C. elegans . (DOCX)
Data
First-order interactors of LAGs in the HLN (without shared genes with WLN) assayed in C. elegans . (DOCX)
Chapter
Full-text available
The expansion of high-throughput technologies have led over the past decade to an unprecedented increase of the pace of data accumulation in biological science at molecular level. However this increase was not even-as while over 2000 genomes are already completed (Pagani et al, 2012) the vast majority of encoded proteins have not yet an assigne...
Article
The Gadd45 proteins have been intensively studied, in view of their important role in key cellular processes. Indeed, the Gadd45 proteins stand at the crossroad of the cell fates by controlling the balance between cell (DNA) repair, eliminating (apoptosis) or preventing the expansion of potentially dangerous cells (cell cycle arrest, cellular senes...
Article
Full-text available
The role of cellular senescence (CS) in age-related diseases (ARDs) is a quickly emerging topic in aging research. Our comprehensive data mining revealed over 250 genes tightly associated with CS. Using systems biology tools, we found that CS is closely interconnected with aging, longevity and ARDs, either by sharing common genes and regulators or...
Article
Full-text available
Although different aspects of cancer immunity are a subject of intensive investigation, an integrative view on the possible molecular links between immunoregulators and cancer-associated genes has not yet been fully considered. In an attempt to get more insights on the problem, we analyzed these links from a network perspective. We showed that the...
Article
Full-text available
Wound healing (WH) is a fundamental biological process. Is it associated with a longevity or aging phenotype? In an attempt to answer this question, we compared the established mouse models with genetically modified life span and also an altered rate of WH in the skin. Our analysis showed that the rate of skin WH in advanced ages (but not in the yo...
Article
In spite of enormous efforts and accumulated knowledge, our capabilities for tackling aging and age-related diseases (ARDs), and ultimately to promote longevity, are still very modest. What is lacking--essential data on key players, efficient analytic tools, or both? Here we discuss how the existing data may be integrated and analyzed in the contex...
Article
Hundreds of genes and miRNAs have been identified as being involved in the determination of longevity, aging patterns and in the development of age-related diseases (ARDs). The interplay between these genes as well as the role of miRNAs in the context of protein-protein interaction networks has as yet been poorly addressed. This work was undertaken...
Article
Full-text available
Gene expression is under a tight epigenetic control which includes DNA methylation, histone modification, and a recently discovered mechanism of RNA interference (RNAi). Not surprisingly, the dysregulations in epigenetic control appear to have a profound impact on both aging and age-related diseases (ARDs) including atherosclerosis, cancer, neurode...
Article
The established human age-related disease proteins (ARDPs) and longevity-associated proteins (LAPs) together with their first-order interacting partners form scale-free networks which significantly overlap. About half of the common proteins are involved in signal transduction. These proteins are strongly interconnected and in turn form a common sig...
Article
An association between aging/longevity and cancer has long been suggested, yet the evolutionary and molecular links between these complicated traits remain elusive. Here, we analyze the relationship between longevity- and cancer-associated genes/proteins (LAGs/LAPs and CAGs/CAPs, respectively). Specifically, we address the following questions: (1)...
Article
Target to template alignment is the limiting accuracy step in Homology Modeling as misalignments by only one residue may result in model errors as large as 4 Å. This step becomes even more critical when sequence identity is lower than 50% and multiple templates are not at hand for multiple alignment analysis. In these cases alignments may be improv...

Network

Cited By

Projects