Physician-scientist - Letter of Motivation for Medical University of Graz, Austria

Hi everyone,

I'm currently preparing my motivational letter for PhD program in Austria.
Any review and feedback will be much appreciated.

Thanks,
Ayu

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Here's the instruction for the motivational letter.
Please provide an original statement why you are interested particularly in the three chosen projects (letter of motivation).

Letter of Motivation

My motivation for applying for this PhD program is to be a skilled and knowledgeable physician-scientist. These combinatory roles as a medical doctor have a synergy in clinical observation and laboratory experiment to solve problems in cancer. The thirst for knowledge and curiosity built from clinical experience encouraged me to seek a scientific explanation for better decision making. For me, a top doctor not only practices a well-established guideline but also thrives for an improvement through a consistent questioning of the status quo of medical care. This also means that a doctor should continuously and actively work through research to answer the question.

Building on two years of research experience and clinical work in Indonesia National Cancer Centre and studying MSc Precision Medicine at University College London (UCL) make me believe that being a doctor and a scientist at the same time would bring benefit not only for me but also for cancer patients around the world. Working under supervisor Dr Karl Kashofer in a research project entitled "cause and consequence of structural DNA damage in cancer" is a way of implementing precision medicine concept and research skills I have learned throughout my master study and contributing to elevate the quality of cancer treatment and to strengthen personalized and tailored decision makings for cancer patients.

My research skills were sharpened when I had an opportunity to work intensely on a multi-omic project as my dissertation. Over the course of 6 months, I strived to excel in the bioinformatic algorithm of RNA sequencing analysis and whole-genome sequencing of the lungs' basal cells and to perform statistical analysis for gene expression-mutational burden correlation. This preliminary project was later successfully announced to be the most impressive project in my program. My wet lab skills were also strengthened during a three-month period in my postgraduate study when I took a hands-on practice in both biomedical and hospital research centre. Needless to say, most of my time during the clinical work and the master study was spent on engaging in scientific writing, to train myself to be a world-class author. Throughout 2 years of my scientific career, I have secured six co-authorships, in both national and international peer-review journals.

My master study equipped me with comprehensive evaluation through genomic, transcriptomic, and epigenetic approach. One finding I discovered in my dissertation is that even before precancer lesion occurs, mutational burden existed and differed among neighbouring basal cells. Two aspects that fascinated me was the low mutational burden happens in the presence of overexpression DNA repair pathways and cells with high mutational burden showed activation of the immune system. What intrigued me after this study is the mechanism of histologically normal tissue expressing more immune-related genes. I speculate that mutational burden contributes to neoantigen expression, therefore allowing for immune response. It is critical considering that DNA damage, dysfunctional DNA repair, and mutational burden trigger and drive carcinogenesis. Pursuing this question may lead to the promotion of immune checkpoint inhibitor and DNA repair restoration. A study by Dr Kashofer entitled "Time series analysis of TP53 gene mutations in recurrent HPV-negative vulvar squamous cell carcinoma" interests me in a way that genetic instability is a dynamic phenomenon thus requiring multiple time investigations. Perhaps, the use of dynamic biomarker is also critical to determine the success of immune checkpoint inhibitor and to measure the extent of the damage of DNA repair. This is potentially implemented in Homologous Recombinant Deficiency (HRD) measurement using either surrogate markers (RAD51, ATM, MRE11 genes) instead of merely HRD score or BRCA positivity or the extent of genomic scars and mutational burden as time series. This is where I believe that the multi-omics analysis that I performed during my master study will be of great advantage to prove that mutational burden, HRD gene markers' expressions, and TCR expression profiling have a correlation. Furthermore, another potential implementation is to measure and calculate the genomic scars and mutational burden at the same time to precisely determine the dose of the immune checkpoint or PARP inhibitor and using this dual therapy for HRD+ cancer. One particularly intriguing for me is that whether the identification of tumour subsets from spatial profiling T cell receptor in tumour tissue among different tumour regions may determine to the extent an individual will benefit from immune therapy.

My second interest is airway remodelling in COPD. Identifying a subset of COPD comprehensively based on microenvironment (immune profiling), clinical data, and histopathology will enable a precise therapeutic approach, an extension of the precision medicine concept. What I found interesting in my dissertation is that inflammatory response and epithelial-mesenchymal transition marked the subset basal cells in the lungs. A susceptibility of some cells to undergo airway remodelling may bring evidence that certain phenotypes benefit from preventive measures, similar to gender as a potential predisposing factor for vascular hypertension in COPD. However, identification of other microenvironment elements, such as fibroblast and extracellular matrix, are important. Also, validation using immunoreactivity test, a co-culture between epithelial cells and immune cells to check cellular interaction, is an approach that worth trying.

Being a PhD student and working in a world-renowned institution such as Medical University Graz would be a dream come true. As one of the universities of excellence in Austria, Medical University Graz would be an encouraging research environment for me. It would provide me with an interdisciplinary and international research collaboration within the translational framework. Furthermore, the integration of laboratory-based research and clinical data analysis in the project would be a suitable platform to apply and upgrade my research skills, enabling one step toward my dream as a physician-scientist. Overall, I believe that my relevant expertise in clinical work and dissertation project combined with a strong motivation and determination would be valuable resources for this PhD program.

Your presentation is a bit confusing. I strongly urge you to reformat the presentation to make each chosen project clearer to the reader. There are 3 research projects you have to present so make the titles of those projects the opening sentence presentation. The only clear project presented was the 2nd project. I was lost as to which was the first and third project choices because of the confusing focus on research, your research abilities, and interest in topics. The reviewer will be looking for clear clues or lead ins to the research projects of interest to you. So bring those upfront in every paragraph. Transition from one project paragraph to the next so that if the reviewer opts to scan your presentation, he can see where one topic ends and another begins. As of now, it appears you have only 2 chosen projects, with one not clearly referred to, out of the required 3. Make sure that you clarify the projects and the purpose of these research. Do not heavily focus on your research abilities. Focus on the research projects instead as that is the main requirement of the prompt. Speak of your related research experiences that will prove your ability to increase your research in the field. How your previous research relates to the new project is more important than over discussing your research skills.