Were you a science curious child? Was there a specific event that sparked your interest in science?
I remember having an appreciation for science as a child. I got a thrill thinking about how large trees are in comparison to people. Then, when the size of the trees sank in, I would think about the size of skyscrapers, and be shocked all over again. I would work my way up, thinking about the universe and the other planets and was amazed that everything on earth was nothing on that scale.
In college I was studying psychology and I learned a theory that proposed that you experience feelings in response to your physical reaction to stimuli. So, smiling is what makes you happy and not the other way around. I thought this was crazy, but it also kind of works! This made me want to understand what exactly was happening at the molecular level to control emotion. I started taking Neuroscience courses and I was sold!
Who do you think made the biggest impact on your development as a scientist from graduate school to postdoctoral training?
My first PI discovered a family of proteins and characterized their function in different biological systems. He dove into whatever field we were studying, and discovered roles for those proteins all over the body. I learned from him that there is exciting science to be found everywhere, if you are clever and keep an open mind!
Give us your elevator pitch. Why is your research important to the ordinary citizen?
I study a cellular self-degradation and recycling process called ‘autophagy’ that is dysfunctional in a number of neurodegenerative diseases, such as Alzheimer’s and Parkinson’s. We currently have no way to stop or reverse the progression of neurodegenerative disease and so, studying the pathways that are dysfunctional is key to finding a cure.
You have transitioned into a postdoctoral role relatively recently. What was your biggest challenge in choosing a laboratory for your training?
For me, the challenge was finding a lab where the basic science was really interesting and also had the potential to be translational. I want to develop drugs to treat disorders of the central nervous system, but I really enjoy researching the biology. When I learned about autophagy and its involvement in neurodegeneration and autism I thought it was an exciting new angle from which we could better understand neurological disease.
As a postdoctoral fellow, what aspects of your position would you like to see improved over the next decade?
Increasing the number of small awards granted to postdocs to fund individual research projects could definitely help postdocs to more freely pursue their own ideas. More small awards can fund pilot studies to produce preliminary data that can then be used for larger grant applications.
Based on your experience in teaching and mentoring, what is the single most important lesson that you aim to convey to trainees?
Keep meticulous records and think about your data! Don’t disregard results because an experiment did not turn out the way you or your PI expected. I have heard a few stories now that begin with a PI telling a trainee there was nothing worth pursuing in a strange finding.
Have you found the manuscript peer review process particularly challenging? What aspects of the process would you like to see improved?
Reading the review for the first time may be the toughest part! I have been pretty lucky so far where the revisions were warranted and have made the paper stronger in the end. I think open access journals have the right idea in making the raw data publicly accessible. I would like to see the data considered during the peer review – I think it would help to uphold the integrity of science publishing.
What aspect of your current research on the process of selective autophagy excites you the most?
We have always wondered why don’t we see the same markers for autophagosomes or induction in response to autophagy activators in neurons as we do in the other cells of the body. In cell lines and non-neuronal tissues, autophagy is robustly induced in response to starvation as a way of recycling cellular components to produce energy. This energy can be used to supply the brain during times of starvation, so it was previously thought that maybe neurons do not use autophagy, or at least not for this purpose. Now we are discovering that autophagy is essential to complex neuron-specific functions such as synaptic plasticity, endocytosis and exocytosis. We are uncovering a pervasive system of autophagy that extends throughout the cell from dendritic spines out to the distal axon. It is very exciting to imagine what we can do if we are able to understand how this system is regulated and target it to treat neurological disease.
There is significant overlap in the specificity of autophagy receptors for various targets. How does this redundancy in specificity impact therapeutic strategies aimed at modulating autophagy?
There is functional redundancy among receptors and Atg8 family members, which definitely adds a surprise factor to research aimed at developing autophagy-modulating therapeutics. This must be taken into account when analyzing results from knock-out mouse models because another receptor may be transcriptionally upregulated to compensate for the loss of the targeted receptor. We have also found receptors that are very structurally similar such as p62 and NBR1 which form heterodimers, though the implications of this interaction is not yet known. As with any rational drug design, we have to judge the efficacy of candidate drugs by looking at effects on the whole system and not just one receptor. Although challenging, the extent of functional redundancy is no surprise given autophagy is a robust system that is fundamental for neuronal homeostasis.
Select Publications by Dr. Kerry Purtell:
Deng Z, Purtell K, Lachance V, Wold MS, Chen S, Yue Z. (2017) Autophagy receptors and neurodegenerative diseases. Trends in Cell Biology. 27(7):491-504.
Purtell K, Gingrich KJ, Ouyang W, Herold KF, Hemmings HC Jr. (2015) Activity-dependent depression of neuronal sodium channels by the general anaesthetic isoflurane. British Journal of Anaesthesia. 115(1):112-21.
Ying SW, Kanda VA, Hu Z, Purtell K, King EC, Abbott GW, GoldsteinPA (2012). Targeted Deletion of Kcne2 Impairs HCN Channel Function in Mouse Thalamocortical Circuits. PLoS One. 7(8):e42756.
Purtell K, Paroder-Belenitsky M, Reyna-Neyra A, Nicola JP, Koba W, Fine E, Carrasco N, Abbott GW (2012). The KCNQ1-KCNE2 K+ channel is required for adequate thyroid I- uptake. FASEB Journal. 26(8):3252-9.
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