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MOTIVATION LETTER

 

I, Lohitesh
K completed Master of Engineering in Biotechnology in July 2017 from Birla
Institute of Technology and Science, Pilani, India. I am writing in response to
your advertisement seeking doctoral position for the project in “CRISPR Screens
for Pro-Oxidant Cancer Therapies” at University of Gothenburg.

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I
did Bachelor
of Technology
in Biotechnology from Vellore Institute of Technology, Vellore, India. My
course as a part of the undergraduate study has helped me in securing a strong
foothold in areas of Cell and Molecular Biology. While studying in bachelor’s, I developed a
particular interest in Cancer Biology during Cell Biology class.  To get in-depth knowledge in cancer, I
have carried out my bachelor’s thesis on “Investigation of phytocompounds for the
treatment of drug resistant Breast cancer: Experimental & Theoretical
approach”. This project gave me valuable experience regarding basics of
designing a study. The importance of considering the variables or factors
affecting the final outcome, identification and optimization of parameters to
achieve the desired result.

 

During
Master’s, I worked on a project titled “The dynamic role of autophagy and MAPK
signaling determines cell fate under cisplatin stress in osteosarcoma cells” to
understand crosstalk between signaling pathways which provided valuable cues to
possible molecular alterations that can be consider for development of improved
therapeutic strategy. In this project, we showed that inhibition of both JNK
and autophagy caused maximal sensitivity to cisplatin. However, there is
altered-regulation of MAPK signaling upon attainment of resistance by these
cells. The role of these MAPKs controlling cell death pathways are gradually
getting understood and hence is crucial to development of appropriate therapies
against parental and resistant cancer cells. After
getting these results, I was inquisitive to decipher the role of autophagy in glioblastoma
because these cells display significant
therapeutic resistance against conventionally used drugs. Therefore,
I have carried out my master’s thesis on “autophagy inhibition potentiates SAHA
mediated apoptosis in glioblastoma cells by accumulation of damaged
mitochondria” to develop potential therapy for glioblastoma multiforme. We
found that the combinatorial treatment of SAHA and CQ result in an increased
damaged mitochondria accumulation in U87MG cells leading to significant
increase in ROS levels and a reduction in mitochondrial membrane potential,
triggering apoptosis.

From my previous work, it is evident that the project is
analogous to the area of interest and thus I wish to continue performing
research in understanding the drug resistance mechanisms
involved in human cancer to discover novel targets and therapeutic agents for
personalized medicine. I am interested in project “CRISPR Screens for
Pro-Oxidant Cancer Therapies” as it involves
detailed dissection of the molecular mechanism of drug effects and resistance
in cancer by using CRISPR/Cas9 platform
and identify phenotypic drivers to develop potential therapy and diagnostic
discriminator for the treatment of cancer. My research interests lie in deciphering
the genesis of drug resistance which helps the tumors to overcome drug
treatments and provide survival advantage. Moreover, I am also interested in
developing drug resistant models and tracking regulation of pathways during
acquisition of resistance to have deeper understanding of the distinctive
genetic signatures and genetic boundaries between untreated cells, drug treated
cells, persisters following drug shock, and persister-derived resistant cells
to design an appropriate therapy. I am keen to elucidate the alterations in ROS
mediated signaling pathways and investigate their contribution in regulating
tumor formation and metastasis which will provide relevant targets in order to
develop innovative and effective therapeutic strategies and hence joining your
group will help me in achieving the same.

 

University
of Gothenburg is a suitable platform for my future research endeavor, giving me
the opportunity to interact and learn from the world-class faculty. I’m eager to take
advantage of the facilities and expertise of this university. The
PhD program in University of Gothenburg shall give me the best of opportunity
to fulfill long term objective of a career in research and education because of
its blend of diverse research and strong pedagogical objectives. To accomplish
this goal, I need wide-ranging exposure and expertise in the landscape of
cancer research that only this course from your University offers. But also want to
contribute with my own expertise and enthusiasm. My previous research experience
has given me the abilities to utilize the resources involved in this
project.  I’ll be proud to be a member of this research
group and represent it through my own publications and other research outputs.

I have successfully published my research work
in international journals. Also, published book chapter on “Cytoplasmic
Signaling Circuitry: An Important Trait of Cancer” in Rediscovering Cancer: From mechanism to
therapy book.  Special
Achievement Award was awarded to me in final year of bachelor’s degree for
meritorious academic performance, research publications and co-curricular
activities.

 

I am confident that my past academic records,
research experiences and career goals have prepared me well for this PhD post.

 

 

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