First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping researchers promote themselves alongside their papers. Amber Shaheen is first author on ‘ Cholesterol is required for activity-dependent synaptic growth’, published in JCS. Amber conducted the research described in this article while a graduate student in Dr Jeffrey Dason's lab at University of Windsor. She is now a MD candidate at Schulich School of Medicine & Dentistry at Western University, London, Canada. Amber's research focuses on understanding the role of cholesterol in neuronal membranes, its regulation by synaptic activity, and its impact on neuronal development and function, using Drosophila as a model organism.

Amber Shaheen

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

In our study, we explored how cholesterol distribution in nerve cells changes in response to neuronal activity. Using specially designed transgenic fruit flies, we found that, when neuronal activity was increased, there was a rise in cholesterol in certain parts of their nerve connections. This increased cholesterol seems crucial for the formation and growth of these connections, especially during periods of high neuronal activity. Interestingly, when we interfered with a molecule called adenylyl cyclase, the nerve connections showed growth impairments that were similar to those observed when cholesterol was reduced, suggesting that these factors might work in tandem. However, when we tried to rescue the growth impairment by increasing another molecule, cAMP (which is produced by adenylyl cyclase), it didn’t have an effect. Additionally, we observed that lower cholesterol levels led to decreased activity of an enzyme called PKA in these nerve connections. Overall, our findings suggest that increased neuronal activity increases cholesterol levels in specific parts of nerve cells, potentially activating a key growth pathway dependent on cAMP and PKA.

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

One of the core challenges we faced during this project revolved around understanding how cholesterol, cAMP and PKA work together. We had a foundational understanding of these components individually. However, understanding how they all fit together was a huge challenge. We had to try many approaches, learning from each attempt. We delved deep into existing literature and conducted a series of experiments, with each trial providing us with valuable insights, even if the outcomes weren't always what we expected. It felt like trying to complete a difficult jigsaw puzzle. But with a lot of hard work, careful note taking, multiple trials and reflection on each step, we gradually built a clearer understanding of the connections among these elements.

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

We opted to submit our manuscript to Journal of Cell Science, which has a long-standing reputation for presenting ground-breaking cellular and molecular biology research. Our investigation explores the role of cholesterol's presence in neuronal membranes, its consequential impacts on neuronal maturation, and overall neuronal functionality. Given the journal's emphasis on cellular mechanisms and their implications in broader biological paradigms, we were confident that our findings regarding the interrelationship between cholesterol, synaptic activity and the cAMP-PKA pathway would be significantly relevant to its dedicated readership.

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

My supervisor, Dr Dason, was essential in guiding me throughout the research process. Beyond the technical guidance in the lab, he consistently offered intellectual and motivational support, especially during the more challenging segments of my project. His profound knowledge and invaluable insights significantly increased my comprehension of the subject. He consistently highlighted the importance of analytical reasoning, which significantly influenced my scholarly approach. I’m super grateful for all the guidance and support he has given me.

Presynaptic terminals aglow with D4H–GFP expression, capturing the complexity of neural communication at the microscopic level.

Presynaptic terminals aglow with D4H–GFP expression, capturing the complexity of neural communication at the microscopic level.

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?

My motivation to pursue a career in science was deeply rooted in a desire to understand the intricate workings of biological systems. My in-depth study of cholesterol’s role in neuronal membranes during my graduate research further fuelled this curiosity. Some standout moments in my journey include overcoming research hurdles with tenacity and embracing a systematic approach to problem solving. Such experiences, coupled with the support of fellow researchers and the excitement of new findings, have guided me to my professional standing and continuously inspired my scientific endeavours.

Who are your role models in science? Why?

My biggest role model in science is Dr Dorothy Andersen, a pathologist and paediatrician known for her contributions to the discovery and description of cystic fibrosis. Her work in the 1930s led to the identification of the disease, and she subsequently developed a diagnostic method for its detection. What's remarkable about her is both her ground-breaking discoveries and her perseverance. Despite facing gender-based challenges in a male-dominated field, Dr Andersen determinedly continued her research. She was among the few women of her time to achieve prominence in medicine and research. Before her work, diseases like cystic fibrosis were often misunderstood. Owing to her perseverance, cystic fibrosis is now more widely recognized, diagnosed, and treated. Her discoveries have paved the way for further research and advancements in the field.

What's next for you?

As my fourth year at Schulich School of Medicine at Western University nears its end, I’ve contemplated my future steps. My journey in medical school has profoundly shaped my perspectives, and I find myself gravitating towards healthcare research. I envision a future where my clinical expertise is supplemented with research, because I believe in the transformative power this holds. Even though I cherish my academic experiences, my heart is set on a path emphasizing research and aiming to bring about impactful medical advancements.

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

From an early age, I've appreciated the finer details of quality stationery. There's a distinct charm in the tactile feel of well-crafted paper and the design of a good pen. Among my most cherished items, vintage fountain pens stand out. They're not just tools for writing; they embody an era of craftsmanship. My collection has grown steadily over the years, each piece reflecting both my professional dedication and profound respect for historical craftsmen.

Amber Shaheen's contact details: Schulich School of Medicine & Dentistry at Western University, 1151 Richmond St, London, ON N6A 5C1, Canada.

E-mail: ashaheen@uwo.ca

Shaheen
,
A.
,
Richter Gorey
,
C. L.
,
Sghaier
,
A.
and
Dason
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J. S.
(
2023
).
Cholesterol is required for activity-dependent synaptic growth
.
J. Cell Sci.
136
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jcs261563
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