Dr Laure Ries
Profiles

Dr Laure Ries

Lecturer in Medical Microbiology

School of Biomedical Sciences (Faculty of Health)

Biography

Biography

2023 - ongoing - Lecturer in Medical Microbiology
2020-2023 Postdoctoral Research Fellow – MRC Centre for Medical Mycology, University of Exeter, UK.
I studied the antagonistic interaction between the opportunistic fungal pathogen Candida albicans and the gram-negative bacterium Serratia marcescens. S. marcescenswas shown to kill C. albicansvia the type 6 secretion system (T6SS), which is a needle like structure that injects effectors into the fungal cell, ultimately killing it. The main research question of this project was how the T6SS can pierce through the fungal cell wall, which presents a formidable and thick barrier to T6SS incursion. I am currently finalising this project.
2017-2020 FAPESP (Sao Paulo Research Foundation) Young Investigator Fellow – Faculty of Medicine, University of Sao Paulo.
2016-2017 CNPq (National Council for Scientific and Technological Development) Postdoctoral Fellow – Faculty of Pharmaceutical Sciences, University of Sao Paulo
From 2016-2021, I was involved in either the supervision or as the primary investigator of several research projects, including the one associated to my fellowship. My research during these years mainly focused on investigating metabolic processes in Aspergillus fumigatusand how they influence pathogenicity. I have briefly listed the most relevant ones hereafter.
I studied the role of the physiologically relevant carbon source acetate for virulence traits of A. fumigatus. Acetate is present in human body fluids and peripheral tissues, and a carbon source for A. fumigatusduring infection. We showed that acetate is metabolized via different pathways in A. fumigatus, a process that is controlled by the previously uncharacterised transcription factor FacB. Furthermore, acetate utilisation significantly affected A. fumigatusvirulence traits such as secondary metabolite secretion and cell wall composition, resulting in altered resistance to oxidative stress, antifungal drugs, and human neutrophil-mediated killing. Indeed, deletion of facBsignificantly impaired the in vivovirulence of A. fumigatusin both insect and mammalian models of invasive aspergillosis (Ries et al., 2021, mBio, doi:10.1128/mBio.01682-21).
I identified a previously uncharacterised transcription factor (termed RglT) as the missing major regulator of gliotoxin (GT) biosynthesis in A. fumigatus. GT is a fungal toxin, which is secreted during the stages of early infection and plays a role in zinc chelation, thus interfering with the normal function of immune cells. In this work, I showed that RglT is important for oxidative stress resistance, GT biosynthesis and self-protection. RglT was shown to be important for virulence in a chemotherapeutic murine model of invasive pulmonary aspergillosis (IPA). Furthermore, I showed that RglT is present in other eurotiomycete and sordariomycete fungi, including the non-GT-producing fungus A. nidulans, where a conservation of function was described (Ries et al., 2020, PLoS Pathog, doi: 10.1371/journal.ppat.1008645).
I supervised a postdoctoral project that aimed at characterising the virulence of Aspergillus nidulans clinical isolates in CGD (chronic granulomatous disease) murine and zebrafish models. This work showed that substantial differences exist between these isolates in terms of genome sequence and structure as well as susceptibility to antifungal drugs and conserved protein kinase signalling pathways (Bastos et al., 2020, mSphere doi: 10.1128/mSphere.00153-20). In addition, I participated in the phenotypic characterisation (antifungal drug susceptibility, growth phenotype, stress resistance, conidia size) of 6 clinical isolates of filamentous fungi from patients with aspergillosis. These isolates turned out to be allodiploid hybrids of two Aspergillusspecies. This was the first time that hybridisation events for human pathogenic fungi were described (Steenwyk et al., 2020, doi: 10.1016/j.cub.2020.04.071).
2013-2016 FAPESP Postdoctoral Fellow – Faculty of Pharmaceutical Sciences, University of Sao Paulo
I investigated the role of different protein domains of the carbon catabolite repressor CreA in Aspergillus nidulansin order to further characterise the secretion of industrially important enzymes. In addition, I studied the regulation of the two transcription factors ClrA and ClrB, important for enzyme secretion in A. nidulans (Ries et al., 2016, doi: 10.1534/genetics.116.187872). 

Qualifications

2008-2012 PhD Fungal Genetics and Molecular Biology - University of Nottingham2005 - 2008 BSc Biological Sciences - University of East Anglia

Professional membership

2022 - present Member of the Microbiology Society
Teaching

Teaching

Teaching interests

Module lead for BHCS001 and BHCS002. 
I also teach on BHCS1006, BHCS2001, BHCS2006, BHCS3003, BHCS5008. 
I primarily teach microbiology with a focus on Mycology and interkingdom interactions. Mycology. Superficial and invasive fungal infections including dermatophytes, commensal and environmental fungi
Interkingdom interactions. Antagonistic or synergistic fungal-bacterial interactions and their impact on human health in a niche-dependent manner. 
Research

Research

Research interests

My research interests primarily lie in studying the interaction between human opportunistic fungal and bacterial pathogens. In particular, I am trying to gain a mechanistic understanding of these interactions as very little is known about what happens at the molecular level in microbial mixed species communities. I am currently working on the gram-negative bacterium Serratia marcescens and the fungus Candida albicans. Both are human opportunistic pathogens, which can be co-isolated from different niches of the human host. S. marcescens uses the type 6 secretion system (T6SS), a needle like structure, to inject C. albicans with effectors, resulting in fungal death (Trunk et al., 2018, doi:10.1038/s41564-018-0191-x). This interaction is antagonistic and physical association between both organisms is absolutely required. Given that the fungal cell wall is a thick and dynamic barrier, that protects C. albicans from a myriad of environmental stresses, we ask the question on how the bacterial T6SS can cross the fungal cell wall to inject the effectors into the target cell. Furthermore, I am also investigating whether the S. marcescens T6SS is effective against Aspergillus fumigatus, a prominent and lethal opportunistic fungal pathogen. In contrast to C. albicans, A. fumigatus is an environmental fungus with a different morphology, cell wall composition and lifestyle.
Lastly, I am studying the interaction between C. albicans and the gram positive bacterium Staphylococcus aureus. S. aureus is a commensal organism of the skin microbiota. C. albicans and S. aureus are the most common agents isolated from bloodstream infections. These dual-species infections often stem from biofilms which are formed in certain disease settings (e.g. the cystic fibrosis lung, periodontitis, burn wound infections) or on abiotic devices such as catheters. Given that interactions between both microorganisms occur in different environments, I am particularly interested on how a particular niche shapes this fungal-bacterial interaction. 

Research degrees awarded to supervised students

Ailton Pereira da Costa Filho – Master of Science (MSc) student, Department of Biochemistry and Immunology, Faculty of Medicine, University of Sao Paulo

Grants & contracts

2023 - MRC CMM Travel Grant, University of Exeter 2023 - Ken Haynes Travel Grant, University of Exeter
2019 - FAPESP (Sao Paulo Research Foundation) SPRINT (Sao Paulo Researcher in INTernational collaboration) project – Faculty of Medicine, University of Sao Paulo (USP) in collaboration with Dr. Mike Bromley from the University of Manchester (UoM).
2017 - FAPESP Young Investigator Fellowship
Publications

Publications

Journals
First author publications:

1. Ries, L.N.A., de Castro, P.A., Pereira Silva, L., Valero, C., dos Reis, T.F., Saborano, R., Duarte, I.F., Persinoti, G.F., Steenwyk, J.L., Rokas, A., Almeida, F., Costa, J.H., Fill, T., Wong, S.S.W, Aimanianda, V., Rodrigues, F.J.S., Goncales, R.A., Duarte-Oliveria, C., Carvalho, A., Goldman, G.H. (2021) Aspergillus fumigatusacetate utilisation impacts virulence traits and pathogenicity. mBio, doi: 10.1128/mBio.01682-21.

2. Ries, L.N.A., Pardeshi, L., Dong, Z., Tang, K., Steenwyk, J.L., Alves de Castro, P., Pereira Silva, L, Colabardini, A.C., Filhi, J.A.F, Preite, N.W., Almeida, F., de Assis, L.J., dos Santos, R.A.C., Bowyer, P., Bromley, M., Owens, R.A., Doyle, S., Demasi, M., Hernandez, D.C.R., Soares Netto, L.E., Pupo, M.T., Rokas, A., Loures, F.V., Wong, K.H., Goldman, G.H. (2020) The Aspergillus fumigatustranscription factor RglT is important for gliotoxin biosynthesis and self-protection, and virulence. PLoS Pathogens, doi: 10.1371/journal.ppat.1008645.

3. Ries, L. N. A., Steenwyk, J. L., de Castro, P. A., de Lima, P. B. A., Almeida, F., de Assis, L. J., Manfiolli, A. O., Takahashi-Nakaguchi, A., Kusuya, Y., Hagiwara, D., Takahashi, H., Wang, X., Obar, J. J., Rokas, A., Goldman, G. H. (2019) Nutritional Heterogeneity Among Aspergillus fumigatusStrains Has Consequences for Virulence in a Strain- and Host-Dependent Manner. Front Microbiol, doi: 10.3389/fmicb.2019.00854.

4. Ries, L. N. A., de Assis, L. J., Rodrigues, F. J. S., Caldana, C., Rocha, M. C., Malavazi, I., Bayram, O., Goldman, G. H. (2018) The Aspergillus nidulanspyruvate dehydrogenase kinases are essential to integrate carbon source metabolism. G3, doi: 10.1534/g3.118.200411.

5. Ries, L. N. A., Beattie, S., Cramer, R. A., Goldman, G. H. (2018) Overview of carbon and nitrogen catabolite metabolism in the virulence of human pathogenic fungi. Mol Microbiol, 107: 277-297. REVIEW

6. Ries, L. N. A., Rocha, M. C., de Castro, P. A., Silva-Rocha, R., Silva, r. N., Freitas, F. Z., de Assis, L. J., Bertolini, M. C., Malavazi, I., Goldman, G. H. (2017) The Aspergillus fumigatusCrzA transcription factor activates chitin synthase gene expression during the caspofungin paradoxical effect. Mbio, volume 8, doi: 10.1128/mBio.00705-17.

7. Ries, L. N. A., Beattie, S. R., Espeso, E. A., Cramer, R. A., Goldman, G. H. (2016) Diverse regulation of the CreA carbon catabolite repressor in Aspergillus nidulans. Genetics, volume 203, pp. 335-352.

8. *Colabardini, A. C.,* Ries, L. N. A., Brown, N. A., Savoldi, M., Dinamarco, T. M., von Zeska, M. R., Goldman, M. H. S. and Goldman, G. H. (2014) Protein kinase C overexpression suppresses calcineurin-associated defects in Aspergillus nidulansand is involved in mitochondrial function. PLOS ONE, volume 9, e104792.

9. Ries, L., Belshaw, N. J., Ilmén, M., Penttilä, M. E., Alapuranen, M. and Archer, D. B. (2013) The role of CRE1 in nucleosome positioning within the cbh1promoter and coding regions of Trichoderma reesei. Appl Microbiol Biotechnol, doi 10.1007/s00253-013-5354-3.

10. Ries, L., Pullan, S. T., Delmas, S., Malla, S., Blythe, M. J., Aboobaker, A. and Archer, D. B. (2013) Genome-wide transcriptional response of T. reeseito lignocellulose using RNA sequencing and comparison with Aspergillus niger. BMC Genomics, volume 14, pp. 541-553.

 

Corresponding author publications:

1. Brauer, V.S., Pessoni, A.M., Freitas, M.S., Cavalcanti-Neto, M.P., Ries, L.N.A., Almeida, F. (2023) Chitin Biosynthesis in Aspergillusspecies. J Fungi, doi: 10.3390/jof9010089.

2. De Castro, P.A., Colabardini, A.C., Moraes, M., Horta, M.A.C., Knowles, S.L., Raja, H.A., Oberlies, N.H., Koyama, Y., Ogawa, M., Gomi, K., Steenwyk, J.L., Rokas, A., Goncales, R.A., Duarte-Oliveira, C., Carvalho, A., Ries, L.N.A., Goldman, G.H. (2022) Regulation of gliotoxin biosynthesis and protection in Aspergillusspecies. PLoS Genet, doi: 10.1371/journal.pgen.1009965.

3. de Assis, L.J., Pereira Silva, L., Bayram, O., Dowling, P., Kniemeyer, O., Kruger, T., Brakhage, A.A., Chen, Y., Dong, L., Tan, K., Wong, K.H., Ries, L.N.A., Goldman, G.H. (2021) Carbon catabolite repression in filamentous fungi is regulated by phosphorylation of the transcription factor CreA. mBio, doi: 10.1128/mBio.03146-20.

4. de Assis, L.J., Pereira Silva, L., Liu, L., Schmitt, K., Valerius, O., Braus, G.H., Ries, L.N.A, Goldman, G.H. (2020) The high osmolarity glycerol mitogen-activated protein kinase regulates glucose catabolite repression in filamentous fungi. PLoS Genet, doi: 10.1371/journal.pgen.1008996.

5. da Costa Filho, A.P., Brancini, G.T.P., de Castro, P.A., Valero, C., Filho, J.A.F., Silva, L.P., Rocha, M.C., Malavazi, I., Pontes, J.G.M., Fill, T., Silva, R.N., Almeida, F., Steenwyk, J.L., Rokas, A., dos Reis, T.F, Ries, L.N.A., Goldman, G.H. (2020) Aspergillus fumigatusG-protein coupled receptors GprM and GprJ are important for the regulation of the cell wall integrity pathway, secondary metabolite production and virulence. mBio, doi: 10.1128/mBio.02458-20.

6. Bastos, R.W., Valero, C., Pereira Silva, L., Schoen, T., Drott, M., Brauer, V., Silva-Rocha, R., Lind, A., Steenwyk, J. L., Rokas, A., Rodrigues, F., Resendiz-Sharpe, A., Lagrou, K., Marcet-Houben, M., Gabaldon, T., McDonnell, E., Reid, I., Tsang, A., Oakley, B. R., Vieira Loures, F., Almeida, F., Huttenlocher, A., Keller, N. P., Ries, L. N. A., Goldman, G. H. (2020) Functional characterization of clinical isolates of the opportunistic fungal pathogen Aspergillus nidulans. mSphere, doi: 10.1128/mSphere.00153-20

7. De Assis, L. J., Manfiolli, A., Mattos, E., Fabri, J. H. T. M., Malavazi, I., Jacobson, I. D., Brock, M., Cramer, R. A., Thammahong, A., Hagiwara, D., Ries, L. N. A., Goldman, G. H. (2018) Protein Kinase A and High-Osmolarity Glycerol Response Pathways Cooperatively Control Cell Wall Carbohydrate Mobilization in Aspergillus fumigatus. Mbio, doi: 10.1128/mBio.01952-18

8. Dos Reis, T. F., Nitsche, B. M., de Lima, P. B. A., de Assis, L. J., Mellado, L., Harris, S. D., Meyer, V., dos Santos, R. A. C., Riaño-Pachón, D. M., Ries, L. N. A., Goldman, G. H. (2017) The low affinity glucose transporter HxtB is also involved in glucose signalling and metabolism in Aspergillus nidulans. Sci Rep, volume 7, doi: 10.1038/srep45073.

9. Dos Reis, T. F., de Lima, P. B., Parachin, N. S., Mingossi, F. B., de Castro Oliveria, J. V., Ries, L. N. A., Goldman, G. H. (2016) Identification and characterization of putative xylose and cellobiose transporters in Aspergillus nidulans. Biotechnol Biofules, volume 9, pp. 204.

Co-author publications:

1. Fabri, J.H., Rocha, M.C., Fernandes, C.M., Persinoti, G.F., Ries, L.N.A., da Cunha, A.F, Goldman, G.H., Del Poeta, M., Malavazi, I. (2021) The heat shock transcription factor HsfA is essential for thermotolerance and regulates cell wall integrity in Aspergillus fumigatus. Front Microbiol, in Press.

2. Johns, L.E., Goldman, G.H., Ries, L.N.A., Brown, N.A. (2021) Nutrient sensing and acquisition in fungi: mechanisms promoting pathogenesis in plant and human hosts. Fungal Biol Rev, doi: 10.1016/j.fbr.2021.01.002

3. de Assis, L.J., Silva, L.P., Bayram, O., Dowling, P., Kniemeyer, O., Kruger, T., Brakhage, A.A., Yingying, C., Dong, L., Tan, K., Wong, K.H., Ries, L.N.A., Goldman, G.H. (2021) Carbon catabolite repression in filamentous fungi is regulated by phosphorylation of the transcription factor CreA. mBio, doi: 10.1128/mBio.03146-20.

4. Steenwyk, J.L., Lind, A.L., Ries, L.N.A., Dos Reis, T.F., Silva, L.P., Almeida, F., Bastos, R.W, de Campos Fraga da Silva, T.F., Bonato, V.L.D., Moreira Pessoni, A., Rodrigues, F., Raja, H.A., Knowles, S.L., Oberlies, N.H., Lagrou, K., Goldman, G.H., Rokas, A. (2020) Pathogenic allodiploid hybrids of Aspergillus fungi. Curr Biol, doi: 10.1016/j.cub.2020.04.071.

5. Drott, M.T., Bastos, R.W., Rokas, A., Ries, L.N.A., Gabaldon, T., Goldman, G.H., Keller, N.P., Greco, C. (2020) Diversity of secondary metabolism in Aspergillus nidulansclinical isolates. mSphere, doi: 10.1128/mSphere.00156-20

6. Antonieto, A. C. C., Nogueira, K. M. V., de Paula, R. G., Nora, L. C., Cassiano, M. H. A., Guazzaroni, M. E., Almeida, F., da Silva, T. A., Ries, L. N. A., de Assis, L. J., Goldman, G. H., Silva, R. N., Silva-Rocha, R. (2019) A novel Cys2His2 zinc finger homolog of AZF1 modulates holocellulase expression in Trichoderma reesei. mSystems, doi: 10.1128/mSystems.00161-19.

7. Mead, M. E., Knowles, S. L., Raja, H. A., Beattie, S. R., Kowalski, C. H., Steenwyk, J. L., Silva, L. P., Chiaratto, J., Ries, L. N. A., Goldman, G. H., Cramer, R. A., Oberlies, N. H., Rokas, A. (2019) Characterizing the pathogenic, genomic and chemical traits of Aspergillus fischeri, a close relative of the major human fungal pathogen Aspergillus fumigatus. mSphere, doi: 10.1128/mSphere.00018-19.

8. Knowles, S. L., Raja, H. A., Wright, A. J., Lee, A. M. L., Caesar, L. K., Cech, N. B., Mead, M. E., Steenwyk, J. L., Ries, L. N. A., Goldman, G. H., Rokas, A., Oberlies, N. H. (2019) Mapping the fungal battlefield: using in situ chemistry and deletion mutants to monitor interspecific chemical interactions between fungi. Front Microbiol, doi: 10.3389/fmicb.2019.00285.

9. De Assis, L. J., Ulas, M., Ries, L. N. A., El Ramli, N. A. M., Sarikaya-Bayram, O., Braus, G. H., Bayram, O., Goldman, G. H. (2018) Regulation of Aspergillus nidulansCreA-mediated carbon catabolite repression by the F-box proteins Fbx23 and Fbx47. Mbio, doi: 10.1128/mBio.00840-18.

10. Beattie, S. R., Mark, K. M. K., Thammahong, A., Ries, L. N. A., Dhingra, S., Caffrey-Carr, A. K., Cheng, C., Black, C. C., Bowyer, P., Bromley, M. J., Obar, J. J., Goldman, G. H., Cramer, R. A. (2017) Filamentous fungal carbon catabolite repression supports metabolic plasticity and stress responses essential for disease progression. PLoS Pathogens, volume 13, e1006340.

11. Brown, N.A., Ries, L.N. A., Reis, T.F., Rajendran, R., Corrêa Dos Santos, R.A., Ramage, G., Riaño-Pachón, D.M., Goldman, G.H. (2016) RNAseq reveals hydrophobins that are involved in the adaptation of Aspergillus nidulansto lignocellulose. Biotechnol Biofuels, volume 9, doi: 10.1186/s13068-016-0558-2.

12. Pereira Silva, L., Alves de Castro, P., Reis, T. F., Paziani, M. H., Von Zeska Kress, M. R., Riaño-Pachón, D.M., Hagiwara, D., Ries, L.N. A., Brown, N.A., Goldman, G.H. (2016) Genome-wide transcriptome analysis of Aspergillus fumigatusexposed to osmotic stress reveals regulators of osmotic and cell wall stresses that are SakAHOG1 and MpkC dependent. Cell Micriobiol, doi: 10.1111/cmi.12681.


Conference Papers
· Ries, L., Belshaw, N. and Archer, D. (2010) Regulation of cellulase gene expression in Trichoderma reesei. Proceedings of IMC9, Edinburgh, P3.217.

· Ries, L., Pullan, S., Delmas, S. and Archer, D. (2012) Comparison of the expression of genes required for carbohydrate deconstruction in Trichoderma reeseiand Aspergillus nigerwhen exposed to wheat straw. Proceedings of the BSBEC Grant holders Workshop, Crewe, p. 112.

· Ries, L.N.A., de Assis, L. J., Brown, N. A. and Goldman, G. H. (2014) Glucose catabolite repression in Aspergillus nidulans. Chosen for oral presentation 5.2. at LIGNOBIOTECH III 3rd Symposium on Biotechnology applied to lignocelluloses.

· Ries, L.N.A. and Goldman, G. H. (2015) Regulation and characterisation of the CreA carbon catabolite repressor in Aspergillus nidulans. Poster 339 at the 28th Fungal Genetics Conference.

· Ries, L.N.A., de Assis, L.J., Santos Rodrigues, F.J., Caldana, C., Rocha, M.C., Malavazi, I., Bayram, O. and Goldman, G.H. (2018) The Aspergillus nidulanspyruvate dehydrogenase kinases are essential to integrate carbon source metabolism. Chosen for oral presentation at the Asperfest15 workshop at the 14th European Conference on Fungal Genetics.

· Ries, L.N.A., de Lima, P.B.A., de Castro, P.A., Pereira Silva, L., Aricetti, J.A. and Goldman, G.H. (2018) Metabolic characterisation of Aspergillus fumigatusclinical isolates. Poster 3 at the 14th European Conference on Fungal Genetics.

· Ries, L.N.A., de Assis, L.J., Santos Rodrigues, F.J., Caldana, C., Rocha, M.C., Malavazi, I., Bayram, O. and Goldman, G.H. (2018) The Aspergillus nidulanspyruvate dehydrogenase kinases are essential to integrate carbon source metabolism. Poster 47 at the 14th European Conference on Fungal Genetics.

· Ries, L.N.A., Pardeshi, L., Araujo, L.R., Colabardini, A.C., Silva, L.P., Almeida, F., de Assis, L.J., dos Santos, R.A.C., Bromley, M., Owens, R., Doyle, S., Demasi, M., Hernandez, D.C.R., Netto, L.E.S., Pupo, M.T., Wong, K.H., Loures, F.V., Goldman, G.H. (2019) The Aspergillus fumigatus transcription factor RglT is crucial for gliotoxin biosynthesis, resistance to oxidative stress and virulence. Poster at the III International Symposium of Fungal Stress (ISFUS)

· Ries, L.N.A., Pardeshi, L., Araujo, L.R., Colabardini, A.C., Silva, L.P., Almeida, F., de Assis, L.J., dos Santos, R.A.C., Bromley, M., Owens, R., Doyle, S., Demasi, M., Hernandez, D.C.R., Netto, L.E.S., Pupo, M.T., Wong, K.H., Loures, F.V., Goldman, G.H. (2019) The Aspergillus fumigatus transcription factor RglT is crucial for gliotoxin biosynthesis, resistance to oxidative stress and virulence. Poster 1500 at the 30th Brazilian Congress of Microbiology.

· Ries, L.N.A., Cherek, P., Hacker, C., Edmondson, M., Bebes, A., Yuecel, R., Quinn, J., Coulthurst, S.J., Gow, N.A.R. (2022) Bacteria-mediated killing of fungi: an opportunity to improve antifungal treatments? Selected oral presentation at the Microbes and Society @Exeter meeting.

· Ries, L.N.A., Cherek, P., Hacker, C., Edmondson, M., Bebes, A., Yuecel, R., Quinn, J., Coulthurst, S.J., Gow, N.A.R. (2022) Fungal-bacterial interactions: the role of the Candida albicanscell wall in resisting killing by the Gram-negative bacterium Serratia marcescens. Selected oral presentation at the 56th British Society for Medical Microbiology (BSMM) Annual Scientific Meeting.

· Ries, L.N.A., Cherek, P., Hacker, C., Edmondson, M., Bebes, A., Yuecel, R., Quinn, J., Coulthurst, S.J., Gow, N.A.R. (2023) Bacteria-mediated killing of Candida albicans: the role of the fungal cell wall in resisting bacterial attack. Selected oral presentation at the Candida and Candidiasis 2023 conference.