First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Melisa Jovita Andrade is first author on ‘RPA facilitates rescue of keratinocytes from UVB radiation damage through insulin-like growth factor-I signalling’, published in JCS. Melisa Jovita is a joint PhD student in the lab of Professor K. Satyamoorthy at Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India and Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia, where her current research interests lie in understanding the cellular responses of skin cells to ultraviolet B radiation (UVBR) and the mechanistic pathways of cellular damage protection by growth factors in 2D and 3D photobiology human skin models.

Melisa Jovita Andrade

How would you explain the main findings of your paper in lay terms?

When human skin is exposed to ultraviolet radiation (UVR) from the sun, it causes damage in the skin cells, which if not repaired may lead to cell death or skin cancer. Several growth factors are produced by the different types of skin cells to carry out host functions. We found that the growth factor IGF-I protects the majority of skin cells even after UVR-induced damage. Typically, various messengers sense the influence of the environment on the skin and transmit signals to facilitate communication with other cells. These messenger molecules in the signalling pathways are responsible for determining the cell fate after UVR damage. Hence, the cells in our skin model systems were exposed to UVR and treated with IGF-I, and then the mechanisms that are involved in UVR protection were studied. This was accomplished by blocking key signalling molecules by rendering genes non-functional. By doing so, we found that a protein called RPA, which facilitates repair and links various essential survival pathways, is among the key players in this complex process and without which IGF-I cannot rescue the skin cells after UVR-induced damage. These findings may have implications in the development of treatment strategies against sunburn or photodamage.

Were there any specific challenges associated with this project? If so, how did you overcome them?

IGF-I rescue experiments in monolayers were relatively straightforward, but as the complexity increased, the influence of other cell types, intracellular crosstalk and ECM factors, among others, made it challenging to comprehensively interpret the resulting findings. Hence, we attempted to systematically introduce a few factors at a time and studied their mechanisms in three photobiology skin models: monolayer keratinocytes (the simplest 2D system), keratinocyte–fibroblast co-cultures (2D systems involving two cell types, facilitating dermal–epidermal crosstalk) and human skin reconstructs (3D systems involving two interacting cell types in a physiologically relevant architecture, consisting of ECM factors and basement membrane).

When doing the research, did you have a particular result or ‘eureka’ moment that has stuck with you?

While it was well-established within our lab and elsewhere that IGF-I treatment before UVR exposure protects skin cells, we were curious whether the protection effect was also observed after UVR exposure. Therefore, we performed preliminary experiments to investigate the effects of IGF-I either pre- or post-UVBR irradiation. Surprisingly, our results showed that post UVBR-induced damage, IGF-I rescues keratinocytes. This was one of the ‘eureka’ moments, which redirected our research work, made us realize that IGF-I induces repair of photoproducts and subsequently led to the finding that a functional RPA protein is essential for IGF-I-mediated rescue.

Why did you choose Journal of Cell Science for your paper?

Since Journal of Cell Science is one of the highly reputed journals covering a broad range of aspects within cell biology, possessing a well-structured and efficient peer-review system and, most importantly, attracting a diverse readership, it was our first choice for communicating our research publication.

RPA is essential for IGF-I-mediated rescue of sunburnt skin. Human skin reconstructs consisting of epidermal keratinocytes and dermal fibroblasts were maintained at the air–liquid interface. Haematoxylin and Eosin staining of these tissue sections after UVBR irradiation and treatment with either IGF-I or IGF-I and RPA inhibitor (TDRL-505), demonstrates reduced sunburnt keratinocytes (marked by arrows), signifying damage rescue in the presence of IGF-I, which is impaired upon TDRL-505 treatment.

RPA is essential for IGF-I-mediated rescue of sunburnt skin. Human skin reconstructs consisting of epidermal keratinocytes and dermal fibroblasts were maintained at the air–liquid interface. Haematoxylin and Eosin staining of these tissue sections after UVBR irradiation and treatment with either IGF-I or IGF-I and RPA inhibitor (TDRL-505), demonstrates reduced sunburnt keratinocytes (marked by arrows), signifying damage rescue in the presence of IGF-I, which is impaired upon TDRL-505 treatment.

Have you had any significant mentors who have helped you beyond supervision in the lab? How was their guidance special?

One of the highlights of pursuing my PhD through a collaborative PhD programme was my remarkable interdisciplinary supervisory team. I have been very fortunate to have wonderful PhD supervisors, particularly Professor K. Satyamoorthy, Dr Derek Van Lonkhuyzen and Dr Zee Upton, who have given me boundless opportunities to grow throughout my PhD tenure. Professor Satyamoorthy has constantly supported me in numerous ways by fuelling my overall scientific curiosity to think outside the box, instilling a forward-thinking attitude and motivating me to work harder. Dr Van Lonkhuyzen has been a source of unwavering support by encouraging me to step out of my comfort zone, sparking thought-provoking discussions and developing a positive outlook that motivated me to do better, both professionally and personally. Dr Zee has been an extremely encouraging associate supervisor, and her inputs were instrumental in shaping my research work. Her insights on interdisciplinary research and innovation have never failed to inspire me. Therefore, each of my supervisors have inculcated in me different values that have immensely contributed towards my all-round development.

What motivated you to pursue a career in science, and what have been the most interesting moments on the path that led you to where you are now?

Well, I have always loved biology, and what could be a better way to understand various aspects of life than to do research? Having said this, I didn't always know what research area I was actually interested in. Initially, during my bachelor's thesis work, I was fascinated with cancer genomics, but over the years, with the broadening of my knowledge and skill set, my research interest has evolved drastically. During my master's thesis, I realized my inclination was towards cell biology-based research and stem cells, gradually developing my passion for tissue engineering and 3D disease modelling. So, it has been a path led by wonderful opportunities, curiosity to experience diverse research areas and pursuit of finding my niche.

Who are your role models in science? Why?

I would say that I do not have a specific role model, but I believe that there is so much we can learn from each and every scientist. Every area of research is important in its own way and deserves credit. Even the smallest contributions to knowledge can make a large impact when we see the bigger picture. In this context, I would like to mention a quote by Sir Issac Newton: “If I have seen further, it is by standing on the shoulders of giants”, that has stuck with me.

What's next for you?

I am currently in the final stages of my PhD, awaiting my final PhD defence, following which I intend to pursue postdoctoral research in the fields of tissue engineering, stem cells and 3D disease modelling.

Tell us something interesting about yourself that wouldn't be on your CV

Since my childhood, I have loved capturing ideas, facial expressions and memories in the form of painting and sketching. Over the years, this has transformed into drawing scientific illustrations, significantly influencing my interest in improving the understanding of complicated scientific concepts through simple colourful illustrations.

Besides sketching, I am passionate about food. I like to try different cuisines and, recently, during the pandemic, I have started trying my hand at cooking, watching YouTube videos. My newfound hobby of being a lockdown chef is something I really enjoy in my free time.

Melisa Jovita Andrade's contact details: Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India; and Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland 4059, Australia

E-mail: melisa.andrade10@gmail.com

Andrade
,
M. J.
,
Van Lonkhuyzen
,
D. R.
,
Upton
,
Z.
and
Satyamoorthy
,
K
. (
2021
).
RPA facilitates rescue of keratinocytes from UVB radiation damage through insulin-like growth factor-I signalling
.
J. Cell Sci.
134
,
jcs255786
.