Imperial College London

DrJoseJimenez Zarco

Faculty of Natural SciencesDepartment of Life Sciences

Senior Lecturer in Synthetic Biology
 
 
 
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Contact

 

j.jimenez

 
 
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Location

 

Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
to

38 results found

Narancic T, Salvador M, Hughes GM, Beagan N, Abdulmutalib U, Kenny ST, Wu H, Saccomanno M, Um J, O'Connor KE, Jiménez JIet al., 2021, Genome analysis of the metabolically versatile Pseudomonas umsongensis GO16: the genetic basis for PET monomer upcycling into polyhydroxyalkanoates, Microbial Biotechnology, Vol: 14, Pages: 2463-2480, ISSN: 1751-7907

The throwaway culture related to the single-use materials such as polyethylene terephthalate (PET) has created a major environmental concern. Recycling of PET waste into biodegradable plastic polyhydroxyalkanoate (PHA) creates an opportunity to improve resource efficiency and contribute to a circular economy. We sequenced the genome of Pseudomonas umsongensis GO16 previously shown to convert PET-derived terephthalic acid (TA) into PHA and performed an in-depth genome analysis. GO16 can degrade a range of aromatic substrates in addition to TA, due to the presence of a catabolic plasmid pENK22. The genetic complement required for the degradation of TA via protocatechuate was identified and its functionality was confirmed by transferring the tph operon into Pseudomonas putida KT2440, which is unable to utilise TA naturally. We also identified the genes involved in ethylene glycol (EG) metabolism, the second PET monomer, and validated the capacity of GO16 to use EG as a sole source of carbon and energy. Moreover, GO16 possesses genes for the synthesis of both medium and short chain length PHA and we have demonstrated the capacity of the strain to convert mixed TA and EG into PHA. The metabolic versatility of GO16 highlights the potential of this organism for biotransformations using PET waste as a feedstock.

Journal article

Vieto S, Rojas-Gatjens D, Jimenez JI, Chavarria Met al., 2021, The potential of Pseudomonas for bioremediation of oxyanions, ENVIRONMENTAL MICROBIOLOGY REPORTS, Vol: 13, Pages: 773-789, ISSN: 1758-2229

Journal article

Hidalgo D, Martínez-Ortiz CA, Palsson BO, Jiménez JI, Utrilla Jet al., 2021, Regulatory perturbations of ribosome allocation reshape the growth proteome with a trade-off in adaptation capacity

<jats:title>Summary</jats:title><jats:p>Bacteria regulate their cellular resource allocation to enable fast growth-adaptation to a variety of environmental niches. We studied the ribosomal allocation, growth and expression profiles of two sets of fast-growing mutants of <jats:italic>Escherichia coli</jats:italic> K-12 MG1655 in glucose minimal medium. Mutants with only 3 of the seven copies of ribosomal RNA operons grew faster than the wild-type strain in minimal media and show similar phenotype to previously studied <jats:italic>rpoB</jats:italic> mutants. Higher growth rates due to increased ribosome content affected resource allocation. Expression profiles of fast-growing mutants shared downregulation of hedging functions and upregulated growth functions. Mutants showed longer diauxic shifts and reduced activity of gluconeogenic promoters during glucose-acetate shifts, suggesting reduced availability of the RNA Polymerase for expressing hedging proteome. These results show that the regulation of ribosomal allocation underlies the growth/hedging phenotypes obtained from laboratory evolution experiments. We show how two different regulatory perturbations (rRNA promoters or <jats:italic>rpoB</jats:italic> mutations) reshape the proteome for growth with a concomitant fitness cost</jats:p><jats:sec><jats:title>Highlights</jats:title><jats:p>Mutants with only 3 ribosomal operons grow faster than wild-type in minimal medium</jats:p><jats:p>Δ4 <jats:italic>rrn</jats:italic> and <jats:italic>rpoB</jats:italic> mutants share phenotypic traits</jats:p><jats:p>Faster growth of mutants is achieved by increased ribosome content</jats:p><jats:p>Fast-growing mutants display reduced hedging expression and adaptation trade-offs</jats:p><jats:p>Despite similar ribosomal content in rich medium the mutants present growth def

Journal article

Kim J, Darlington APS, Bates DG, Jimenez JIet al., 2021, The interplay between growth rate and nutrient quality defines gene expression capacity

<jats:title>Abstract</jats:title><jats:p>The gene expression capacity of bacterial cells depends on the interplay between growth and the availability of the transcriptional and translational machinery. Growth rate is widely accepted as the global physiological parameter controlling the allocation of cell resources. This allocation has an impact on the ability of the cell to produce both host and heterologous proteins required for synthetic circuits and pathways. Understanding the relationship between growth and resources is key for the efficient design of artificial genetic constructs, however, it is obscured by the mutual dependence of growth and gene expression on each other. In this work, we investigate the individual contributions of molecular factors, growth rate and metabolism to gene expression by investigating the behaviour of bacterial cells growing in chemostats in growth-limited conditions. We develop a model of the whole cell that captures trade-offs in gene expression arising from the individual contributions of different factors, and validate it by analysing gene couplings which emerge from competition for the gene expression machinery. Our results show that while growth rate and molecular factors, such as the number of rRNA operons, set the abundance of transcriptional and translational machinery available, it is metabolism that governs the usage of those resources by tuning elongation rates. We show that synthetic gene expression capacity can be maximised by using low growth in a high-quality medium. These findings provide valuable insights into fundamental trade-offs in microbial physiology that will inform future strain and bioprocesses optimisation.</jats:p>

Journal article

González J, Salvador M, Özkaya Ö, Spick M, Reid K, Costa C, Bailey MJ, Avignone-Rossa C, Kümmerli R, Jimenez Zarco Jet al., 2020, The loss of the pyoverdine secondary receptor in Pseudomonas aeruginosa results in a fitter strain suitable for population invasion, The ISME Journal: multidisciplinary journal of microbial ecology, Vol: 15, Pages: 1330-1343, ISSN: 1751-7362

The rapid emergence of antibiotic resistant bacterial pathogens constitutes a critical problem in healthcare and requires the development of novel treatments. Potential strategies include the exploitation of microbial social interactions based on public goods, which are produced at a fitness cost by cooperative microorganisms, but can be exploited by cheaters that do not produce these goods. Cheater invasion has been proposed as a ‘Trojan horse’ approach to infiltrate pathogen populations with strains deploying built-in weaknesses (e.g., sensitiveness to antibiotics). However, previous attempts have been often unsuccessful because population invasion by cheaters was prevented by various mechanisms including the presence of spatial structure (e.g., growth in biofilms), which limits the diffusion and exploitation of public goods. Here we followed an alternative approach and examined whether the manipulation of public good uptake and not its production could result in potential ‘Trojan horses’ suitable for population invasion. We focused on the siderophore pyoverdine produced by the human pathogen Pseudomonas aeruginosa MPAO1 and manipulated its uptake by deleting and/or overexpressing the pyoverdine primary (FpvA) and secondary (FpvB) receptors. We found that receptor synthesis feeds back on pyoverdine production and uptake rates, which led to strains with altered pyoverdine-associated costs and benefits. Moreover, we found that the receptor FpvB was advantageous under iron-limited conditions but revealed hidden costs in the presence of an antibiotic stressor (gentamicin). As a consequence, FpvB mutants became the fittest strain under gentamicin exposure, displacing the wildtype in liquid cultures, and in biofilms and during infections of the wax moth larvae Galleria mellonella, which both represent structured environments. Our findings reveal that an evolutionary trade-off associated with the costs and benefits of a versatile pyoverdine uptake

Journal article

Lastiri-Pancardo G, Mercado-Hernandez JS, Kim J, Jimenez JI, Utrilla Jet al., 2020, A quantitative method for proteome reallocation using minimal regulatory interventions (Jul, 10.1038/s41589-020-0593-y, 2020), NATURE CHEMICAL BIOLOGY, Vol: 16, Pages: 1277-1277, ISSN: 1552-4450

Journal article

Lastiri-Pancardo G, Mercado-Hernandez JS, Kim J, Jimenez JI, Utrilla Jet al., 2020, A quantitative method for proteome reallocation using minimal regulatory interventions, NATURE CHEMICAL BIOLOGY, Vol: 16, ISSN: 1552-4450

Journal article

González J, Salvador M, Özkaya Ö, Spick M, Costa C, Bailey MJ, Avignone-Rossa C, Kümmerli R, Jiménez JIet al., 2020, The loss of the pyoverdine secondary receptor in Pseudomonas aeruginosa results in a fitter strain suitable for population invasion

<jats:title>Abstract</jats:title><jats:p>The rapid emergence of antibiotic resistant bacterial pathogens constitutes a critical problem in healthcare and requires the development of novel treatments. Potential strategies include the exploitation of microbial social interactions based on public goods, which are produced at a fitness cost by cooperative microorganisms, but can be exploited by cheaters that do not produce these goods. Cheater invasion has been proposed as a ‘Trojan horse’ approach to infiltrate pathogen populations with strains deploying built-in weaknesses (e.g. sensitiveness to antibiotics). However, previous attempts have been often unsuccessful because population invasion by cheaters was prevented by various mechanisms including the presence of spatial structure (e.g. growth in biofilms), which limits the diffusion and exploitation of public goods. Here we followed an alternative approach and examined whether the manipulation of public good uptake and not its production could result in potential ‘Trojan horses’ suitable for population invasion. We focused on the siderophore pyoverdine produced by the human pathogen <jats:italic>Pseudomonas aeruginosa</jats:italic> MPAO1 and manipulated its uptake by deleting and/or overexpressing the pyoverdine primary (FpvA) and secondary (FpvB) receptors. We found that receptor synthesis feeds back on pyoverdine production and uptake rates, which led to strains with altered pyoverdine-associated costs and benefits. Moreover, we found that the receptor FpvB was advantageous under iron-limited conditions but revealed hidden costs in the presence of an antibiotic stressor (gentamicin). As a consequence, FpvB mutants became the fittest strain under gentamicin exposure, displacing the wildtype in liquid cultures, and in biofilms and during infections of the wax moth larvae <jats:italic>Galleria mellonella</jats:italic>, which both represent structured e

Journal article

Kim J, Darlington A, Salvador M, Utrilla J, Jimenez Jet al., 2020, Trade-offs between gene expression, growth and phenotypic diversity in microbial populations, CURRENT OPINION IN BIOTECHNOLOGY, Vol: 62, Pages: 29-37, ISSN: 0958-1669

Journal article

Lastiri-Pancardo G, Mercado-Hernandez JS, Kim J, Jiménez JI, Utrilla Jet al., 2019, A quantitative method for proteome reallocation using minimal regulatory interventions

<jats:title>Abstract</jats:title><jats:p>Engineering resource allocation in biological systems for synthetic biology applications is an ongoing challenge. Wild type organisms allocate abundant cellular resources for ensuring survival in changing environments, reducing the productivity of engineered functions. Here we present a novel approach for engineering the resource allocation of <jats:italic>Escherichia coli</jats:italic> by rationally modifying the transcriptional regulatory network of the bacterium. Our method (ReProMin) identifies the minimal set of genetic interventions that maximise the savings in cell resources that would normally be used to express non-essential genes. To this end we categorize Transcription Factors (TFs) according to the essentiality of the genes they regulate and we use available proteomic data to rank them based on its proteomic balance, defined as the net proteomic charge they release. Using a combinatorial approach, we design the removal of TFs that maximise the release of the proteomic charge and we validate the model predictions experimentally. Expression profiling of the resulting strain shows that our designed regulatory interventions are highly specific. We show that our resulting engineered strain containing only three mutations, theoretically releasing 0.5% of their proteome, has higher proteome budget and show increased production yield of a molecule of interest obtained from a recombinant metabolic pathway. This approach shows that combining whole-cell proteomic and regulatory data is an effective way of optimizing strains in a predictable way using conventional molecular methods.</jats:p><jats:sec><jats:title>Importance</jats:title><jats:p>Biological regulatory mechanisms are complex and occur in hierarchical layers such as transcription, translation and post-translational mechanisms. We foresee the use of regulatory mechanism as a control layer that will aid in t

Journal article

Salvador M, Abdulmutalib U, Gonzalez J, Kim J, Smith AA, Faulon J-L, Wei R, Zimmermann W, Jimenez JIet al., 2019, Microbial Genes for a Circular and Sustainable Bio-PET Economy, GENES, Vol: 10, ISSN: 2073-4425

Journal article

Salvador M, Abdulmutalib U, Gonzalez J, Kim J, Smith AA, Faulon J-L, Zimmermann W, Jimenez JIet al., 2019, Genes for a Circular and Sustainable Bio-PET Economy

<jats:p>Plastics have become an important environmental concern due to their durability and resistance to degradation. Out of all plastic materials, polyesters such as polyethylene terephthalate (PET) are amenable to biological degradation due to the action of microbial polyester hydrolases. The hydrolysis products obtained from PET can thereby be used for the synthesis of novel PET as well as becoming a potential carbon source for microorganisms. In addition, microorganisms and biomass can be used for the synthesis of the constituent monomers of PET from renewable sources. The combination of both biodegradation and biosynthesis would enable a completely circular bio-PET economy beyond the conventional recycling processes. Circular strategies like this could contribute to significantly decrease the environmental impact of our dependence on this polymer. Here we review the efforts made towards turning PET into a viable feedstock for microbial transformations. We highlight current bottlenecks in the degradation of the polymer and the metabolism of the monomers and we showcase fully biological or semisynthetic processes leading to the synthesis of PET from sustainable substrates.</jats:p>

Journal article

Darlington APS, Kim J, Jimenez JI, Bates DGet al., 2018, Engineering Translational Resource Allocation Controllers: Mechanistic Models, Design Guidelines, and Potential Biological Implementations, ACS SYNTHETIC BIOLOGY, Vol: 7, Pages: 2485-2496, ISSN: 2161-5063

Journal article

Darlington APS, Kim J, Jimenez JI, Bates DGet al., 2018, Dynamic allocation of orthogonal ribosomes facilitates uncoupling of co-expressed genes, NATURE COMMUNICATIONS, Vol: 9, ISSN: 2041-1723

Journal article

Darlington APS, Kim J, Jiménez JI, Bates DGet al., 2018, Engineering Translational Resource Allocation Controllers: Mechanistic Models, Design Guidelines, and Potential Biological Implementations

<jats:title>Abstract</jats:title><jats:p>The use of orthogonal ribosomes in combination with dynamic resource allocation controllers is a promising approach for relieving the negative effects of cellular resource limitations on the modularity of synthetic gene circuits. Here, we develop a detailed mechanistic model of gene expression and resource allocation, which when simplified to a tractable level of complexity, allows the rational design of translational resource allocation controllers. Analysis of this model reveals a fundamental design trade-off; that reducing coupling acts to decrease gene expression. Through a sensitivity analysis of the experimentally tuneable controller parameters, we identify how each controller design parameter affects the overall closed-loop behaviour of the system, leading to a detailed set of design guidelines for optimally managing this trade-off. Based on our designs, we evaluated a number of alternative potential experimental implementations of the proposed system using commonly available biological components. Finally, we show that the controller is capable of dynamically allocating ribosomes as needed to restore modularity in a number of more complex synthetic circuits, such as the repressilator, and activation cascades composed of multiple interacting modules.</jats:p>

Journal article

Cavaliere M, Feng S, Soyer OS, Jimenez JIet al., 2017, Cooperation in microbial communities and their biotechnological applications, ENVIRONMENTAL MICROBIOLOGY, Vol: 19, Pages: 2949-2963, ISSN: 1462-2912

Journal article

Qian Y, Huang H-H, Jimenez JI, Del Vecchio Det al., 2017, Resource Competition Shapes the Response of Genetic Circuits, ACS SYNTHETIC BIOLOGY, Vol: 6, Pages: 1263-1272, ISSN: 2161-5063

Journal article

Darlington APS, Kim J, Jiménez JI, Bates DGet al., 2017, Dynamic allocation of orthogonal ribosomes facilitates uncoupling of co-expressed genes

<jats:title>Abstract</jats:title><jats:p>Introduction of synthetic circuits into host microbes creates competition between circuit and host genes for shared cellular resources, such as RNA polymerases and ribosomes. This can lead to the emergence of unwanted coupling between the expression of different genes, complicating circuit design and potentially leading to circuit failure. Here we demonstrate the ability of orthogonal ribosomes to alleviate the effects of this resource competition. We partition the ribosome pool by expressing an engineered 16S RNA with altered specificity, and use this division of specificity to build simple resource allocators which reduce the level of ribosome-mediated gene coupling. We then design and implement a dynamic resource allocation controller, which acts to increase orthogonal ribosome production as the demand for translational resources by a synthetic circuit increases. Our results highlight the potential of dynamic translational resource allocation as a means of minimising the impact of cellular limitations on the function of synthetic circuitry.</jats:p>

Journal article

Jimenez JI, 2017, Shedding light on the black box models of the cell, MICROBIAL BIOTECHNOLOGY, Vol: 10, Pages: 43-45, ISSN: 1751-7915

Journal article

Avendano R, Chaves N, Fuentes P, Sanchez E, Jimenez JI, Chavarria Met al., 2016, Production of selenium nanoparticles in Pseudomonas putida KT2440, SCIENTIFIC REPORTS, Vol: 6, ISSN: 2045-2322

Journal article

Xulvi-Brunet R, Campbell GW, Rajamani S, Jimenez JI, Chen IAet al., 2016, Computational analysis of fitness landscapes and evolutionary networks from in vitro evolution experiments, METHODS, Vol: 106, Pages: 86-96, ISSN: 1046-2023

Journal article

Kim J, Salvador M, Saunders E, Gonzalez J, Avignone-Rossa C, Jimenez JIet al., 2016, Properties of alternative microbial hosts used in synthetic biology: towards the design of a modular chassis, SYNTHETIC BIOLOGY-BOOK, Vol: 60, Pages: 303-313, ISSN: 0071-1365

Journal article

Gyorgy A, Jimenez JI, Yazbek J, Huang H-H, Chung H, Weiss R, Del Vecchio Det al., 2015, Isocost Lines Describe the Cellular Economy of Genetic Circuits, BIOPHYSICAL JOURNAL, Vol: 109, Pages: 639-646, ISSN: 0006-3495

Journal article

Jimenez JI, Fraile S, Zafra O, de Lorenzo Vet al., 2015, Phenotypic knockouts of selected metabolic pathways by targeting enzymes with camel-derived nanobodies (VHHS), METABOLIC ENGINEERING, Vol: 30, Pages: 40-48, ISSN: 1096-7176

Journal article

Nilgiriwala KS, Jimenez J, Rivera PM, Del Vecchio Det al., 2015, Synthetic Tunable Amplifying Buffer Circuit in E. coli, ACS SYNTHETIC BIOLOGY, Vol: 4, Pages: 577-584, ISSN: 2161-5063

Journal article

Jimenez JI, Perez-Pantoja D, Chavarria M, Diaz E, Lorenzo Vet al., 2014, A second chromosomal copy of the catA gene endows Pseudomonas putidamt-2 with an enzymatic safety valve for excess of catechol, ENVIRONMENTAL MICROBIOLOGY, Vol: 16, Pages: 1767-1778, ISSN: 1462-2912

Journal article

Freese PD, Korolev KS, Jimenez JI, Chen IAet al., 2014, Genetic drift suppresses bacterial conjugation in spatially structured populations

<jats:p>Conjugation is the primary mechanism of horizontal gene transfer that spreads antibiotic resistance among bacteria. Although conjugation normally occurs in surface-associated growth (e.g., biofilms), it has been traditionally studied in well-mixed liquid cultures lacking spatial structure, which is known to affect many evolutionary and ecological processes. Here we visualize spatial patterns of gene transfer mediated by F plasmid conjugation in a colony of Escherichia coli growing on solid agar, and we develop a quantitative understanding by spatial extension of traditional mass-action models. We found that spatial structure suppresses conjugation in surface-associated growth because strong genetic drift leads to spatial isolation of donor and recipient cells, restricting conjugation to rare boundaries between donor and recipient strains. These results suggest that ecological strategies, such as enforcement of spatial structure and enhancement of genetic drift, could complement molecular strategies in slowing the spread of antibiotic resistance genes.</jats:p>

Journal article

Freese PD, Korolev KS, Jimenez JI, Chen IAet al., 2014, Genetic Drift Suppresses Bacterial Conjugation in Spatially Structured Populations, BIOPHYSICAL JOURNAL, Vol: 106, Pages: 944-954, ISSN: 0006-3495

Journal article

Fraile S, Jimenez JI, Gutierrez C, de Lorenzo Vet al., 2013, NanoPad: An integrated platform for bacterial production of camel nanobodies aimed at detecting environmental biomarkers, PROTEOMICS, Vol: 13, Pages: 2766-2775, ISSN: 1615-9853

Journal article

Jimenez JI, Xulvi-Brunet R, Campbell GW, Turk-MacLeod R, Chen IAet al., 2013, Comprehensive experimental fitness landscape and evolutionary network for small RNA, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 110, Pages: 14984-14989, ISSN: 0027-8424

Journal article

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