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Interview with our ESRs

Our ESRs Sonnal Lohia and Hubert Krukowski respond to our questions regarding their experience as students of the STRATEGY-CKD project.


 


Can you tell us about your background and what motivated you to pursue a PhD in the field of chronic kidney disease (CKD)?

Hello, my name is Sonnal Lohia, and I am the ESR5 at the “STRATEGY-CKD” consortium, located at the Biomedical Research Foundation, Academy of Athens in Greece. I would like to start by answering the first part of your question.


I completed my bachelor’s in Biotechnology in India, where I developed a keen interest in working with analytical instruments and learning about their importance in research. Later, I moved to Germany to pursue my master’s in Agricultural Food Production. During my master’s program, I had the opportunity to conduct several research projects in various departments and laboratories across Germany. Coincidentally, all these research projects involved the application of various analytical tools, both experimental and statistical. These experiences ignited a passion for research within me, and by the end of my master’s, I was undoubtedly keen on pursuing a career in academia, which led me to pursue a PhD.


Now, to answer the second part of your question: Why CKD in particular? Let me take you back to when I was 14 years old, and my beloved grandfather was suddenly admitted to the hospital. He underwent coronary bypass surgery, and despite the success of the surgery, he was diagnosed with End Stage Renal Disease (ESRD). Both his kidneys stopped functioning, and before we could fully understand the diagnosis, he passed away within a week of the surgery. Although I never expressed it vocally, I was deeply driven to understand the field of biomedical sciences from that moment, wanting to make a significant difference, however small it might be. Therefore, when I came across the “STRATEGY-CKD” consortium and their efforts in developing novel therapies and drug targets for CKD, I knew I had found exactly what I was unconsciously seeking.


What are your research objectives in the STRATEGY-CKD project?

Initially, my research objective was to focus on identifying gut microbiome-produced proteins and peptides that vary in CKD patients by analyzing well-characterized biological samples such as fecal samples using high-resolution state-of-the-art proteomic technologies like liquid chromatography coupled with mass spectrometry (LC-MS) and bioinformatic analysis. As my work progressed, the research objective became more specific: identifying host and bacterial proteins from fecal suspension samples of early and advanced CKD stage patients. This identification was conducted using a combination of GeLC-MS sample preparation, LC-MS/MS analysis, and Proteome Discoverer 1.4 software, employing both Human and Bacterial databases. Through statistical analysis, I observed significant changes in the proteins at the two CKD stages, and these observations were contextualized biologically through bioinformatic analyses.


What are the key findings or contributions you've made to the project so far? Can you describe any challenges you've encountered and how you've overcome them?

At the start of my PhD, I wrote a review paper combining all omics studies analyzing the interplay between the gut microbiota and CKD. Interestingly, all these studies highlighted damages to gut barrier integrity, linking it to reduced butyrate concentrations observed in CKD. In my dissertation, the identified human and bacterial proteins collectively indicated the presence of inflammation and reduced saccharolytic fermentation, which plausibly reduced butyrate synthesis and eventually affected gut barrier integrity in advanced kidney disease stages.


I think it is safe to say that this is the first study identifying human and bacterial proteins from fecal suspension samples in CKD. However, this novelity came with its own set of challenges, such as a very low sample size for the two disease stages, optimizing the protocol for sample preparation through numerous preliminary analyses, and finalizing the database for this meta-proteomic search. Surprisingly, while many fecal proteomics studies on fecal samples are published, the reproducibility factor for the databases used in these studies was relatively low. Another challenge was not just finding but also successfully applying bioinformatic analysis tools for this meta-proteomics approach. These challenges are possible reasons why meta-proteomics studies lag behind meta-genomics studies.


In your opinion, what are some of the most pressing challenges in the field of CKD research?

The first challenge is in the diagnosis of the disease. Currently, both eGFR and albumin levels have more diagnostic value only in the advanced stages of CKD, highlighting the need for new reliable biomarkers to diagnose pre-CKD stages, which is where most research is focused today. The second challenge is identifying the underlying molecular mechanisms of the disease, a very time-consuming process that requires extensive trial and error approaches. The third challenge is the complexity of CKD. It has been linked to Type II Diabetes Mellitus, cardiovascular diseases, obesity, hypertension, and now changes in the gut microbiota. Hence, any research cannot solely focus on CKD without considering all associated complications, making it a highly challenging and tedious process for any single research group.


In my opinion, collaborations, sharing research objectives, and publishing failures by research groups worldwide are ways to accelerate CKD research while addressing these challenges. In this context, the STRATEGY-CKD consortium successfully united research groups from the EU, focusing collectively on the interplay between the gut microbiota and CKD and its many aspects.


How did you collaborate with other ESRs within the consortium, and what has been the most rewarding aspect of working in a multidisciplinary team?

My most significant collaboration in this project was with Sophie (ESR1, UGENT), who provided prepared fecal suspension samples and performed a verification study by ELISA to quantify specific protein levels in the fecal samples. This was alongside several rounds of discussions on experiment design, analysis results, and manuscript preparation. I also collaborated with Emmanouil (ESR3, MOS), who played an essential role in guiding me through developing R scripts for the peptidomic analysis. Additionally, I had fruitful discussions with Federica (ESR2, UKA), Hubert (ESR6, VIB-VZW), Yuselys (ESR8, UNIV VANVITELLI), and Piotr (ESR11, RDN), which helped finalize my project’s research objectives.

Coming from India, working in a multidisciplinary team exponentially increased my integration into the working culture of the EU. Understanding various perspectives and different problem-solving approaches has been the most rewarding aspect of these collaborations.


Can you share any memorable experiences or highlights from your involvement in the project?

I have made many memories in the last three years, making it difficult to choose just a few. Scientifically, participating in and presenting my research at conferences organized by ERA and EMBL counts as an achievement. Personally, all the in-person meetings conducted by the STRATEGY-CKD consortium were highlights of my experience. These conferences and in-person meetings not only validated my research efforts but also inspired and motivated me to continue working hard.


What opportunities for training and professional development have you received through the MSCA-ITN project, and how has this influenced your career aspirations?

I grasp topics faster and more in-depth by listening to lectures or witnessing practical applications. In this regard, the workshops and training conducted as part of the consortium were particularly helpful for me in understanding CKD, its complications, and the gravity of this silent epidemic. Additionally, these workshops introduced me to many research groups across the EU, motivating me to continue my career in academia and manifesting my desire to be a part of them. Furthermore, the opportunity to organize and present in web-seminars with participants from over 10 different countries has undoubtedly honed my organization and presentation skills.



 


Can you tell us about your background and what motivated you to pursue a PhD in the field of chronic kidney disease (CKD)?

I began my academic journey with a BSc in Biomedical Sciences from the Edinburgh Napier University. During my undergraduate studies, I developed a keen interest in the microbiome and its critical role in human health. This interest deepened as I pursued my MSc in Biotechnology at the University of Strathclyde where my research focused on the intricate relationships between diet, the microbiome, and chronic diseases.

It was during this period that I became particularly interested in CKD. Despite CKD affecting a significant portion of the population, it remains under-discussed and often overlooked. This gap in attention and research motivated me to delve into this area further. The intersection of microbiome research and CKD presents a unique opportunity to explore innovative ways to understand and potentially mitigate the impact of this disease.

By pursuing a PhD, I aim to deepen my understanding and contribute to advancements in CKD research, particularly through the lens of microbiome interactions. I believe that this work has the potential to lead to significant improvements in patient outcomes and public health.


What are your research objectives in the STRATEGY-CKD project?

In the STRATEGY-CKD project, my primary research objectives are centered around investigating the bidirectional links between CKD and the gut microbiome. Specifically, I aim to understand how CKD influences the composition and functionality of the gut microbiome and, conversely, how alterations in the gut microbiome impact the progression and severity of CKD.


What are the key findings or contributions you've made to the project so far? Can you describe any challenges you've encountered and how you've overcome them?

So far, my contributions to the STRATEGY-CKD project have been both collaborative and foundational. While my key findings will be detailed in my first original research publication, which is soon to be submitted, I have already made significant contributions through collaborative efforts.


One of the notable contributions is co-authoring a comprehensive review article with my colleagues Sophie from UGent and Avra from Danone. In this review, we set guidelines for conducting CKD microbiome studies, addressing the methodological challenges and proposing standardised approaches to improve the reliability and reproducibility of research in this field. This article also discusses the current challenges faced in CKD microbiome research, such as the variability in microbiome sampling and analysis, and proposes strategies to overcome these obstacles.


Among the challenges I encountered, one of the primary ones has been the inherent variability in microbiome data due to differences in patient populations, diets, and medications. To address this, we have emphasisd the importance of standardizsd protocols and have advocated for multi-center collaborations to ensure more robust and generalisable findings.


In your opinion, what are some of the most pressing challenges in the field of CKD research?

In the field of CKD research, one of the most pressing challenges is the early detection of the disease, as current biomarkers and screening methods often fail to identify CKD until it has significantly progressed. Another major challenge is the heterogeneity of CKD, which complicates the development of universal treatment strategies and requires a deeper understanding of the different subtypes and their specific mechanisms. Research into the gut microbiome's role in CKD is still in its early stages, and uncovering the precise mechanisms of its influence remains a significant hurdle. Additionally, the variability in microbiome data due to patient diversity and methodological differences poses a challenge for reproducibility and generalisability in research findings. Finally, addressing disparities in research participation and ensuring that studies include diverse populations is critical for developing treatments that are effective across all demographics.


How did you collaborate with other ESRs within the consortium, and what has been the most rewarding aspect of working in a multidisciplinary team?

Collaboration with other ESRs within the consortium has been a highly rewarding aspect of my work. I had the opportunity to co-author a review article with partners from UGent and Danone in the Netherlands, which was particularly fulfilling. This collaboration allowed us to combine our diverse expertise and set important guidelines for CKD microbiome studies. Additionally, working with other ESRs on various projects has been invaluable, as it provided a platform for mutual learning and knowledge exchange. The most rewarding aspect of working in a multidisciplinary team is the ability to draw from a wide range of perspectives and skills, which has greatly enriched my research and broadened my understanding of the field.


Can you share any memorable experiences or highlights from your involvement in the project?

One of the most memorable experiences from my involvement in the project was the training event organised by Utrecht University. During this event, we not only deepened our understanding of CKD but also had the opportunity to visit the nephrology unit at the local hospital. Meeting patients receiving dialysis and hearing their personal stories was particularly impactful. Speaking with a patient about her experiences living with CKD brought a profound human element to our research, reminding me to always consider the person behind the sample number. This experience has stayed with me and continually motivates me to pursue research that can make a real difference in patients' lives.


What opportunities for training and professional development have you received through the MSCA-ITN project, and how has this influenced your career aspirations?

Through the project, I have had the privilege of attending a variety of highly valuable training sessions organised both by the consortium and my local institutions. These sessions have covered a wide range of topics, from advanced research methodologies to professional skills development. Additionally, I have had the opportunity to attend conferences that focused not only on renal health but also on the microbiome and diet. These experiences have been instrumental in broadening my knowledge and keeping me updated with the latest advancements in these fields.


Moreover, these opportunities have allowed me to network with professionals and researchers from various institutions, all working towards the common goal of improving health outcomes for people. This exposure has significantly influenced my career aspirations by highlighting the importance of interdisciplinary collaboration and reinforcing my commitment to contributing to impactful research that can improve patient lives.


We thank Sonnal and Hubert for their participation!

 

 

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