My PhD Journey – Dr. M Aimanuddin Mohtar

Photo: Enjoying the rare sunshine at the Meadows, Edinburgh with lab members

After spending nearly 6 years in the United States for my Bachelors and Masters, I decided that I was going to settle down and find a decent job in Malaysia. But that was not the case. Circa 2012, I stumbled upon the UMBI website while doing a little bit of research on Malaysia’s background in the Molecular Biology and Biotechnology fields. At that time (I still do, now), I personally thought that UMBI has one of the best facilities and laboratories in Molecular Biology and Medicine in Malaysia, and notably, it houses The Malaysian Cohort Biobank, the largest repository of biospecimens in the country. I tried my luck and applied for a research fellow position in UMBI. Shortly after, I was selected for an interview. Unfortunately, I was told during the interview that the position is for a PhD holder. Nevertheless, I was offered the new fellowship scheme from UKM with a full scholarship abroad if I wanted to further my PhD. After the completion of my PhD, I would then be hired as a research fellow in UMBI. After thinking for a long time, I decided to accept the offer, though I would have to leave my family and country for the third time.

I chose to work in the field of cancer because it is one of the most notorious medical diseases which has been studied extensively in the era of modern medicine. Cancer is generally deemed a single disease, but in fact, it is not. There are more than 200 types of cancer, each type is different and has a unique genetic landscape which would require its own specific approach for treatment. My interest to work in cancer fits well with UMBI’s core research theme. I applied to several labs working on cancer biology in the UK (away from London). Professor Dr Ted Hupp from University of Edinburgh, UK replied to my application. After a chat with him and inspired by his excellent track record of publishing in over 130 international peer-reviewed interdisciplinary journals, I determined to join his lab. Professor Hupp is the Chair of Experimental Cancer Research and group leader for the cancer cell signalling unit at the Institute of Genetics and Molecular Medicine, University of Edinburgh, UK. I had another strong reason for joining his team: the lab is located in the historic city of Edinburgh, capital city of Scotland, and houses one of the best medical school in the UK. Professor Hupp himself did his post-doc in the famous lab of David Lane, working on the p53 tumour suppressor protein.

Photo: Cancer cell signalling unit annual Christmas dinner

I embarked on the journey of my PhD on October 2013. This time I was not alone because I brought along my newly-wedded wife, who supported me immensely during my studies. During the early days, I was given several projects where I would later choose one which best suit my interest and has the potential to be developed into a PhD thesis. I decided to study the biology of the anterior gradient-2 protein (AGR2), a protein which the lab has been studying for more than 10 years. AGR2 is an endoplasmic reticulum-resident protein that is a member of the protein disulphide isomerase (PDI) superfamily. It has been postulated as a clinically important protein as it is upregulated in various types of cancer and demonstrated tumour-promoting features. The role of AGR2 is not fully understood, and it is the aim of my thesis to elucidate the role of AGR2 in cancer development. I focused on identifying novel AGR2 interacting proteins (termed interactome) by looking at the functional consequences of some of these interactions to deduce the role of AGR2. I used two approaches to identify the AGR2 interactome; 1) database mining of AGR2 sequence-specific peptide motif; 2) quantitative mass spectrometry analysis of cell models with a controlled expression of AGR2. The key AGR2 client proteins were then validated using both in-vitro and cell-based assays. I also developed synthetic tools to further dissect the pro-oncogenic role of AGR2. These tools include: 1) developing AGR2 monoclonal antibodies in the format of the scFv fragment; 2) engineering synthetic mini-protein containing AGR2 sequence-specific peptide motif and; 3) engineering synthetic membrane proteins that optimally bind to AGR2. This work leads to the notion that AGR2 has a novel role in cancer cell signalling: it possesses an intrinsic sequence-specific peptide binding for a subset of its client proteins, and one function of this motif is to ensure proper maturation of client proteins for their final destination.

During the course of my PhD, I have been exposed to many laboratory techniques such as protein purification, confocal microscopy, peptide-phage display, and protein-protein interaction assays. I was the first lab member of the lab to try out the CRISPR/Cas9 genome editing tools for my project. Additionally, I had the chance to work on hydrogen-deuterium mass spectrometry with our collaborators in Czech Republic. I was also involved in mentoring exchange students from Germany (Erasmus), India, and A*Star Singapore.  Towards the end of my PhD, I presented my work at a conference in Girona, Spain. I managed to finish my thesis and successfully ‘survived’ my viva in March 2017.

Photo: The iconic Scottish Great Highland bagpipe near Edinburgh Castle

Overall, it has been a challenging journey for me, yet a very wonderful and memorable experience. I received tremendous support from my team members and especially from my supervisor who gave me valuable advice. Professor Hupp prefers the term ‘encouraging results’ in otherwise disastrous experimental failures – this has kept me going when results were not forthcoming. More importantly, I was blessed with having my first child in Scotland; she cheered me every day, her growth and development mirroring my PhD journey. I am now back in Malaysia and about to start my lab at UMBI. I hope I can contribute as much as I can to cancer research and impart the experience that I have had in Edinburgh to UMBI and to help develop UMBI as one of the finest cancer research institutes in the country.


M Aimanuddin Mohtar, PhD