Postdoctoral Research Fellow at the University of Nottingham
By Vipul Batra
Vipul completed a B.Sc. and M.Sc. in System Biology and Bioinformatics at the Panjab University and a PhD in Animal Biotechnology from ICAR-NDRI, India. Currently a postdoctoral researcher at the University of Nottingham, he explores how a father’s diet influences gamete quality, embryonic development, maternal health, fetal growth, and the lifelong health of offspring. His research focuses on whether extracellular vesicles (EVs) from the male reproductive tract play a role in parental programming under the Developmental Origins of Health and Disease (DOHaD) paradigm.
My journey as a Postdoc had been replete with eclectic failures which, nonetheless, led me to discover a novel class of extracellular vesicles (EVs) in the male reproductive tract (MRT). This blog post aims to highlight that failure can serve as a powerful opportunity for growth and embracing it is the key to success.
Background of the setbacks
A part of my research includes isolating EVs from various MRT segments e.g. testes, epididymis, seminal vesicles and semen. We then characterize these vesicles and the biomolecular cargo/payload carried by them including RNAs, proteins and metabolites – by omics and other relevant techniques. We started with EVs isolated from the seminal vesicles fluid. The seminal vesicles glands produce approximately 90% of the ejaculate volume in mice underscoring their substantial contribution to the semen composition. We had previously noted changes in the transcriptomic and proteomic profiles of sperm and seminal plasma when exposed to suboptimal diets and we aimed to explore whether these changes were influenced by the cargo of seminal vesicle fluid EVs (Svf-EVs). These Svf-EVs had the typical cup-shaped, round morphology and size of that of conventional EVs – step one passed! The next step was isolating proteins and RNA from them, however, every LC-MS/MS (a method used to detect proteins) run detected 10-15 random mostly irrelevant proteins despite being quantified by two distinct methods. We tried it more than a couple of times switching from the conventional LC-MS/MS to zSWATH DIA (an advanced method of detecting proteins), but alas – no avail! Nonetheless, this confirmed the absence of any substantial proteomic cargo within these EVs. I then decided to move to RNA-Seq (a method used to detect RNAs) and the failure followed me there as well. Analysis of RNA content via the high-sensitivity RNA assays failed to detect any RNA.
By this time, I was completely frustrated from wasting time, resources, money and energy. I developed imposter syndrome and started doubting my abilities, keeping to myself, thinking my labmates were judging me, and struggling with my mental health.
Resilience & Role (of PI)
My (amazing!) supervisor, Adam, and I decided to move on to explore other MRT-derived EVs for the time being. He suggested and motivated me to join numerous workshops and courses for personal and professional growth. For example, one of them was on how to overcome the sense of academic failure and it made me realize that everyone fails. I thank him for putting his trust in me and motivating me to attend those. They helped. A lot! I acquired skills which would be helpful in my career progression trajectory and helped me to introspect and know myself better. This invigorated me and we started again.
We isolated EVs from the caput and cauda epididymis segments (epididymosomes) and subjected them to a similar characterization strategy as followed for Svf-EVs. We detected more than a thousand proteins and hundreds of short non-coding RNAs (miRNA, piRNA etc.) in these epididymosomes. Voila! This was the Eureka moment for us since this meant that the Svf-EVs were non-conventional and atypical being marked by the absence of transcriptomic and proteomic cargo. Interestingly, we also found that the expression of characteristic EV markers (tetraspanin proteins) in these Svf-EVs was distinct from the epipididymosomes at single vesicle resolution!
Outcome
Svf-EVs may be a novel class of non-canonical EVs that may carry a distinctive cargo composition. We recently identified >500 distinctive metabolites in these EVs. However, we do not know if their production is a component of the normal cellular homeostasis process or if a non-cargo component is involved in crosstalk within the female reproductive tract. Unravelling their functional significance is imperative to understand their role in reproductive physiology and paternal programming of offspring health.
Lessons learnt
- Failure is inevitable, learn to embrace it
Science, like many areas in life, involves embracing uncertainty and learning from failure. Every researcher will face failed experiments—just as anyone in their career will hit roadblocks. But failures are where the learning happens. Instead of getting stuck, try something different. Eat, sleep, work out, and go again!
- Failure is fruitful
Overcoming setbacks is what drives progress, both in science and in life. Each challenge builds resilience and deepens your understanding, not just of your field, but of yourself. Innovation often emerges from what initially appears to be a failure.
- Admit that you failed
The first step toward success is acknowledging when something doesn’t work. Talk to others—there’s no shame in asking for help. We all fail, and it’s through sharing those experiences that we grow.
It is human to err (and judge!). Remember, being judged by others is part of the process, but it’s how you judge yourself that matters. Trust your abilities and keep moving forward.
