BUILD series 2. PhD times and Postdoc

This is a BUIDL series about company building, a collection of personal stories that led me to creating 100XBIO. The article is a twin to my 29-min YouTube video posted here: https://youtu.be/Ng8m2Ue9X1c The video gives plenty of context that most people don't need and would not find interesting, so this article is a shortened summary.

In this article, I discuss the challenges I faced during grad school and my postdoc.

Introduction to My PhD Journey

It’s Sergei from 100XBIO. In this article, I continue my story about why I started a PhD in Immunology of Infection. Previously, I talked about my school years and how I got into grad school in Russia, where I worked on developing a targeted drug against tuberculosis.

Research Focus and Drug Development

The concept involved attaching isoniazid, a drug that kills mycobacteria, to a biologically inert polysaccharide dextran. This conjugate was intended to deliver isoniazid to cells that take up dextran. The idea seemed underdeveloped, but some in vivo data suggested that this conjugate was effective in treating tuberculosis in mice. The studies used BCG, a strain of M. tuberculosis, which can induce liver and lung fibrosis. I was given the task to study the potential of the modified dextran to prevent fibrosis, as this condition poses significant medical challenges with no proven methods to stop it.

Writing a Review Paper and Challenges

To explore different ideas, I needed to develop a review paper on the mechanisms of action and how dextran could prevent fibrosis. I began learning how to write scientific publications through a Coursera course from Stanford, which helped me understand effective scientific communication. However, a lack of mentorship from experienced researchers hindered my ability to publish in reputable journals. I decided to take on multiple jobs, including scientific translation, to support my learning.

Investigating Receptor-Dependent Mechanisms

I investigated how dextran interacts with macrophages and identified receptors that could bind dextran. My hypothesis was that if dextran occupied these receptors, it could shift the immune response to bacteria from anti-inflammatory to pro-inflammatory, potentially reducing fibrosis. This approach was misaligned with my current organization’s focus, which sought a direct antifibrotic action. Consequently, I connected with the Novosibirsk Tuberculosis Research Institute, which hired me to test my hypothesis.

International Collaborations

At the new institute, I received excellent support for my project despite limited funding. I joined international societies and found a mentor who helped improve my research and provided valuable insights. I spent half a year conducting joint research at Drexel University, which significantly advanced my work. I published a review paper and explored the potential of dextran to block HIV entry into cells.

Postdoctoral Experience and Career Decisions

After my PhD, I joined a lab that was focused on cancer immunology. I recognized the similarities between chronic infections and cancer, particularly in immune evasion. During my postdoc, I considered various career paths, including consulting and many other industry roles. I sought informational interviews to understand where I could best leverage my skills. I was inspired by webinars from the Cheeky Scientist Association. Ultimately, I concluded that becoming an industry scientist was the best path for me.

Future Directions

In the next article, I will share insights about my first industry job and how it led to the creation of my company, 100XBIO. Thank you for reading, and I look forward to sharing more of my journey with you.

P.S. Here is the link to my review article about dextran and its receptors, "Targeting the C-type lectins-mediated host-pathogen interactions with dextran"

https://pubmed.ncbi.nlm.nih.gov/25224349/

It was a nice experience publishing at the Journal of Pharmacy & Pharmaceutical Sciences, https://www.frontierspartnerships.org/journals/journal-of-pharmacy-pharmaceutical-sciences