GRADUATE & LIFE SCIENCES EDUCATION

Ingrid Grozavu, Biochemistry

 

Student Name: Ingrid Grozavu
Department: Biochemistry
Research Title: Mapping KRAS signalling pathways using the Mammalian Membrane Two-Hybrid (MaMTH) assay to elucidate novel therapeutic targets.
Supervisor:  Dr. Igor Stagljar

Description of your research:
My goal is to find new vulnerabilities of KRAS-driven cancers using a proteomics-based approach. The KRAS oncogene is one of the largest problems in oncology. It is commonly mutated in three of the four most lethal cancers in North America, namely lung, colorectal, and pancreatic cancer. It is also altered in 25-30% of all human cancers. Unfortunately, no clinically-effective drugs exist to target KRAS despite its disease burden, suggesting that its biology is more complicated than previously thought. Therefore, I am working towards mapping the interactome of KRAS in its wildtype and oncogenic forms. To achieve this, I’ll be using the Mammalian Membrane Two-Hybrid (MaMTH) assay, which detects protein-protein interactions of any integral- or membrane-associated protein. Using MaMTH, I am screening the human ORFeome library, consisting in ~14,000 cDNAs, to determine which proteins KRAS interacts with. Altogether, this data will reveal the comprehensive and dynamic interactome of KRAS, and expose vulnerabilities within its protein interaction network.


Why did you choose this department:
I knew I wanted to continue working in the same lab where I did my 4th-year thesis project. Dr. Stagljar was affiliated with the Biochemistry and Molecular Genetics departments. Since I was part of Molecular Genetics during my undergraduate years, I decided I wanted to try something new and join the Biochemistry department.


How was your experience looking for a research opportunity:
Starting out was difficult – I had received different advice from friends and classmates, and some of it even conflicted! Ultimately, I found that understanding the PIs research was the most crucial step to take before applying for lab positions. Not only did I get a higher response rate, I also ended up enjoying the projects I was working on.


When did you start your research experience:
I started off in the summer after my first year in the Fantus Lab in Physiology. Being a first-year student, I didn’t have the skills to take on a research project of my own. However, I helped out with general lab chores and assisted graduate students with easier tasks. This helped me to learn some techniques and understand how labs operate. I used this knowledge to secure lab positions in subsequent summers. In my final year, I joined the Stagljar Lab and fell in love with the research conducted here, and decided to stay for grad school!


Why did you choose this supervisor:
Igor is an awesome supervisor and mentor, and the research he coordinates is ground-breaking, so staying in his lab was a no-brainer. I also enjoy working with members of the lab. Everyone is very approachable, and has their particular area of expertise. When there’s an experiment that doesn’t work or a specific question you have, you know who to ask first based on their background. Our lab also partakes in collaborations, and I saw this as a way to explore what other groups are researching while also linking my project to other experts.


What’s your experience with research:
Answering one question often results in many new questions. For example, I’ll do an experiment and find that my protein of interest, KRAS, affects a signalling pathway differently based on how much stimulus I apply to the cell. Next, a million questions start to build: Where is the tipping point for this stimuli to change KRAS behaviour? Does this happen in other similar stimuli? Do those have similar tipping points? What other proteins are involved in modifying the behaviour of KRAS as a result from this stimulus? How does KRAS affect other proteins as a result of this stimulus, and how does this behaviour change based on the amount of stimulus?


This process does get a bit tedious sometimes. But, I enjoy problem-solving and thinking about how different puzzle pieces fit together.

How’s the social experience with research:
Our lab is located in an open-concept building, so meeting members from other labs is very easy. Also, as a graduate student, I fall under multiple student organizations, such as the Biochemistry Graduate Student Union, the Donnelly Centre Graduate Student Association, GLSE, and so forth. These unions organize events to facilitate interactions between graduate students, so there is always an event around the corner to meet new people.


What are your future career plans:
I am certain I want to take on a leadership role, though I haven’t yet decided what that will look like. I am currently focused on my graduate studies and getting as much as I can out of the program. I hope that by the time I finish my PhD, I will have learned a plethora of techniques, writing and communication skills, and further improved my critical thinking.


I am also involved in entrepreneurship – I am working on putting together a startup in the assay development field. Through this experience, I am learning how to become more adaptable to changing situations, how to find opportunities, how to network, etc.

Combined, I think that these two experiences will together expand my personal and professional development in a complementing way. Not only can I cross-apply what I learn from each project, but these will help me become an effective leader in my career.

Quote:
There are two quotes I’d like to share:


“Any idiot can make a decision with perfect information. But, in real life you will always have limited information. Don’t wait until you have perfect information – learn how to make decisions early.” From Reza Satchu (2017).

“Years ago, my mother used to say to me "In this world, Elwood, you must be oh so smart or oh so pleasant." Well, for years I was smart. I recommend pleasant.” From the movie Harvey (1950).

Tip:
Always add one more control in your experiment!!