PeerJ Award Winners at XVII FISV Congress

by | Nov 6, 2024 | Award Winner Interviews

More than 400 Italian scientists active in the field of Life Sciences convened in Padua from 18 to 20 September for the XVII Congress of the Italian Federation of Life Sciences (FISV),  a non-profit organisation representing 18 Italian scientific societies and associations. The FISV Congress provides a unique opportunity for Italian scientists to delineate prospective scenarios for future research projects in Life Sciences and promote interdisciplinary and intergenerational exchange.  The three-day event comprised three keynote lectures, eight symposia, six mini-symposia, six poster presentations, two round tables designed to facilitate interaction between scientists and non-scientists, and an event dedicated to young researchers.

The Italian Federation of Life Sciences (FISV) has infact launched in January 2024 a training programme entitled “FISVforYoung” to disseminate information regarding the latest technological developments, to impart skills that will enable participants to address fundamental questions in Life Sciences, and to foster cohesion and collaboration among Italian young scientists. During the Congress, more than 200 young scientists had the unique opportunity to present their work: here are interviews from those awarded for the Best Oral Presentations.

 

Renée Duardo Post-Doctoral Researcher at Alma Mater Studiorum – University of Bologna, Italy.

Can you tell us a bit about yourself and your research interests?

I first studied at the University of Calabria, where I obtained my bachelor’s degree in Biology. Then, I moved to the University of Bologna, where I graduated in Molecular and Cellular Biology in 2018. After graduation, I was accepted into a PhD program in the Laboratory of Cancer Genome Instability at the University of Bologna, Department of Pharmacy and Biotechnology, under the supervision of Professor Giovanni Capranico. During my PhD, I worked on several projects related to non-B DNA structures, such as R-loops and G-quadruplexes. My PhD project specifically focused on understanding how Topoisomerase 1 regulates R-loops, and how the formation of these structures affects chromatin organization, genome functions and stability, ultimately leading to micronuclei formation. Currently, I am working as a Postdoctoral Researcher in the same laboratory supported by the AIRC (Triennial Fellowship ‘Guglielmina Lucatello e Gino Mazzega’). As a Postdoc, my research focuses on RNA Polymerase II backtracking and the potential formation of downstream R-loops as a primary mechanism of Topoisomerase 1-related instability at early replication regions, leading to increased DNA damage and micronuclei formation.

What first interested you in this field of research?

What first interested me in this field of research was the opportunity to explore drugs already known and used in chemotherapy (Topoisomerase1 poisons), in order to better understand the fundamental biological processes underlying their mechanisms of action, with the hope of making discoveries that could eventually improve treatments and medical outcomes.

Can you briefly explain the research you presented at FISV 2024?

I am happy to share that the research I presented at the FISV congress has recently been published in Science Advances (DOI: 10.1126/sciadv.adm8196). In this work, by integrating genomic maps of DNA-RNA hybrids and DNA damage, we identified genomic sites of Top1cc-associated double-strand breaks (DSBs), likely resulting from DNA-RNA hybrids downstream of arrested RNAPII and transcription-replication collisions (TRCs), leading to fork collapse, DNA cleavage, and micronuclei formation. Here the link for a summarizing video

How will you continue to build on this research?

Our next goals for this project are to further characterize this class of R-loops and to determine whether our newly proposed mechanism of Top1cc-induced TRCs and genome instability, involving RNAPII arrest, can be leveraged to improve the efficacy of Topoisomerase 1 poisons.

 

Suleman Khan Zadran Post-Doctoral research fellow at Alma Mater Studiorum – University of Bologna, Italy.

Can you tell us a bit about yourself and your research interests?

I am a Cellular and Molecular Biologist with a specific focus on mechanistic studies, epigenetics, and functional genomics, particularly in the context of cancer biology. My work revolves around understanding the molecular underpinnings of neuroblastoma (NB), an aggressive pediatric cancer. Over the course of my academic and professional journey, I’ve developed expertise in advanced gene-editing techniques, such as CRISPR-Cas9, and explored the potential of nanomedicine and synthetic biology for neuroblastoma therapy.

Currently, my research interests center on two main projects: investigating the epigenetic mechanisms that confer resistance to anti-GD2 immunotherapy in NB, and studying the role of the B7-H3 protein in the initiation and progression of NB. I also maintain a strong interest in developing novel therapeutic strategies to overcome cancer resistance, combining my skills in functional genomics and molecular biology to identify promising new drug targets.

What first interested you in this field of research?

My fascination with cancer biology began during my early academic years, driven by the complexity of how cancer cells evade the body’s immune system and traditional therapies. This curiosity led me to pursue a PhD in Cellular and Molecular Biology at the University of Bologna, where I became particularly captivated by NB, a type of cancer that predominantly affects children and has limited treatment options.

What solidified my passion was the realization that while significant progress has been made in understanding cancer, many challenges remain, especially in pediatric cancers like NB. The potential to use technologies such as CRISPR-Cas9 gene editing to directly intervene at the molecular level and nanomedicine to deliver targeted therapies opened up new possibilities for advancing treatments. The combination of scientific challenges and the opportunity to develop therapies that could truly make a difference in patients’ lives was irresistible to me.

Can you briefly explain the research you presented at FISV 2024?

At the FISV Congress, I presented my research focused on developing a novel therapeutic platform using the M13 bacteriophage as a vector for targeted photodynamic therapy (PDT) against NB. The primary aim was to exploit the specificity of the GD2, which is over-expressed in many solid tumors including NB to selectively target and destroy tumor cells.

We engineered the M13 phage to display an anti-GD2-specific single-chain variable fragment (scFv) on its surface, allowing it to selectively bind to GD2-positive NB cells. In addition, we functionalized the phage with photosensitizers (PS), which, upon exposure to light, generate reactive oxygen species (ROS) that can kill cancer cells. Our results demonstrated that the engineered phage efficiently penetrated GD2-positive tumor spheroids and induced over 95% cell death upon light activation, without harming GD2-negative cells. Importantly, the phage bioconjugates were also shown to deeply penetrate in GD2-positive tumor spheroids and to induce spheroid breakdown and cell death upon irradiation. Finally, we devised a CRISPRi strategy to overcome resistance mediated by loss of the GD2 expression, correlating with poor prognosis in NB patients. These results provide for the first time a minimally invasive strategy to target NB tumors and their microenvironment with high efficiency, along with a straightforward strategy to overcome anti-GD2 resistance.

This research not only highlights the potential of using bacteriophage-based platforms for cancer therapy but also underscores the importance of precision medicine and targeting anit-GD2-resistant NB.

How will you continue to build on this research?

The next steps in my research will involve further optimizing and refining the M13 phage-based platform to enhance its therapeutic efficacy. One of the key challenges in cancer treatment is overcoming resistance mechanisms, and I aim to delve deeper into the epigenetic factors that contribute to the resistance of NB cells to both immunotherapies and photodynamic therapies. I plan to expand the use of CRISPR-Cas9 technology, employing both knock-in and knockout screening to identify the transcription factors that regulate resistance, thereby revealing novel targets for therapeutic intervention.

In parallel, I will continue my investigation into the B7-H3 protein’s role in neuroblastoma progression. B7-H3 is emerging as a significant immunoregulatory molecule in cancer, and understanding its role could lead to the development of new treatment strategies. By elucidating the molecular pathways involving B7-H3, I hope to uncover potential biomarkers for cancer progression and novel drug targets that could improve patient outcomes.

Ultimately, my goal is to translate these preclinical findings into therapies that can be tested in clinical trials, with the long-term vision of providing more effective, targeted treatment options for NB patients. Collaborating with fellow researchers and clinicians will be crucial as I move forward, and I’m excited about the potential impact this research could have on the future of cancer therapy.

Anna Santin Post-Doctoral Researcher at the University of Padua, Italy.

Can you tell us a bit about yourself and your research interests?

I began my academic journey studying photosynthesis in microalgae, which inspired my curiosity about plant metabolism. Later, during my PhD, I focused on nitrogen transport and metabolism in diatoms, and how they affect cell homeostasis and growth. Currently, as a postdoctoral researcher, my work aims to bridge these two fields. I am investigating the interplay between nitrogen metabolism and photosynthesis, as well as how nitrogen affects carbon metabolism and vice versa. This integrated approach enables me to explore the dynamic balance between key biochemical processes in microalgae, which have great potential to understand the importance of their ecological role and to improve microalgal productivity and sustainability in a context of biotechnological applications.

What first interested you in this field of research?

What initially fascinated me about this field was the desire to understand the molecular mechanisms behind fundamental but complex metabolic processes. Nitrogen and carbon metabolisms are at the core of ecological and potential biotechnological advancements in plant science. Understanding how these two metabolic pathways are linked can reveal new approaches to optimizing growth of microalgal cultures, which are reaching even more attention in the last years.

Can you briefly explain the research you presented at FISV 2024?

At the FISV Congress, I presented research on the metabolic interplay between nitrogen and carbon assimilation in Anabaena sp. PCC7120, a diazotrophic cyanobacterium. In this filamentous organism, nitrogen fixation occurs in heterocysts, while vegetative cells generate carbon skeletons through photosynthesis. Our work explored how these two cell types coordinate their metabolic roles. We performed a detailed analysis of photosynthetic activity, exposing filaments to varying metabolic conditions and observing how cells adjust photosynthetic components and electron pathways in response to changes in nitrogen assimilation.

How will you continue to build on this research?

Following this research line, we are employing genetically encoded fluorescence probes to monitor in vivo specific intracellular metabolic variations. These probes can help reveal the dynamic interaction between nitrogen and carbon metabolism in diazotrophic cyanobacteria but not only, showing how different cell types maintain homeostasis through metabolic coordination.

Stefania Mattevi PhD candidate at the University of Brescia, Italy.

Can you tell us a bit about yourself and your research interests?

Currently I am a PhD student at the Molecular and Translational Medicine Department at the University of Brescia in the computational biology lab led by Prof. Paolo Martini. My research focuses on developing a computational approach called ASTRA (Allelic Specific Transcriptional Regulation Analysis), organized as an automatized workflow, enabling integrated analysis of Allele Specific Expression (ASE) and/or Allele Specific Accessibility from bulk RNA-seq data.

What first interested you in this field of research?

My first interest in the field raised from the perspective to develop a tool to provide a genome-wide snapshot of the transcriptional landscape and enhance our understanding of determinants of allelic expression at both bulk and single-cell levels.

Can you briefly explain the research you presented at FISV 2024?

Cardiomyopathies (CMs) are diseases of the myocardium that lead to structural and functional cardiac abnormalities. Despite three decades of research into their genetic etiology, variable expressivity and incomplete penetrance remain largely unresolved issues. Allele Specific Expression (ASE) analysis can contribute to shed light on the latter. In fact, in dilated cardiomyopathy (DCM), cis-regulatory variants have been shown to contribute to observed phenotypic heterogeneity. Applying ASTRA to a DCM cohort revealed intriguing insights into the expression patterns of key genes associated with CMs, such as monoallelic expression of TNNI3, MYBPC3, and ITGB1 in distinct patients.

How will you continue to build on this research?

We aim at the publication of ASTRA as a publicly available tool following the development of a robustand user-friendly version with tutorial and case studies.

 

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