Yensi Flores Bueso. Image: Tomas Tyner
Dr Yensi Flores Bueso overcame institutional and societal challenges to develop a successful career in cancer research.
Computation protein design is “a paradigm shift in biology”, says Dr Yensi Flores Bueso, “offering unprecedented control over creating proteins tailored to specific applications”.
As Bueso explains, proteins are the workforce of the cell, “responsible for nearly every biological process, with their shapes determining their functions – much like a key and keyhole”.
“For decades, we worked to modify existing natural proteins, trying to repurpose them for new functions they weren’t originally designed for. This was akin to reshaping an existing key to fit a different lock – a process that was often inefficient and limited.
“Now, with computational protein design, we have the capability to design entirely new synthetic proteins that don’t exist in nature. These proteins can be custom-built for specific applications, making them far more efficient and perfectly suited to their intended purpose … essentially designing the perfect key for any door we wish to open.”
Bueso is a Marie Curie postdoctoral research fellow at the Institute for Protein Design (IPD) at the University of Washington and the Cancer Research lab at University College Cork (UCC), where she designs photosynthetic electron transfer systems and bacteriotherapy for solid tumours.
As well as her day job, where she has already made significant contributions to cancer research, Bueso aims to remove barriers to research for underrepresented regions, by reforming research assessment systems, promoting research integrity and fostering trust in science. Among the many initiatives she is involved with, Bueso is co-lead of the Global Young Academy, where she organises workshops and panels, and co-led the largest, most diverse study to date on academic promotion practices, which was just published in Nature.
“Throughout my journey, I have worked in diverse contexts, including those with limited resources, requiring creativity, self-learning and securing funding,” Bueso says.
“For instance, during my final year of undergraduate studies, I founded the first molecular biology lab at the National University of Honduras, despite never formally studying molecular biology. This perspective has inspired me to launch initiatives where research addresses societal challenges.”
Tell us about your current research.
During my PhD, I developed a strong interest in computational protein design while working on bacteria-delivered therapeutics for solid tumours.
A key challenge for the success of this therapeutic modality is balancing the safety of non-pathogenic (probiotic) bacteria, which minimise immune responses, with their limited ability to deliver therapeutic biomolecules intracellularly due to the impermeable cell membrane. I am trying to address this challenge with computational protein design.
Initially, I proposed engineering chimeric proteins capable of crossing cell membranes. However, this remains a challenging task and is still being explored through various strategies by colleagues at IPD.
While there is no one-size-fits-all method for delivery that can be universally adopted for any protein, a highly complex natural system, developed by bacteria, can enable this process – bacterial contractile injection systems.
Very recently, some studies have successfully borrowed and engineered these systems into biotechnology strains such as E coli, which serves as a proof of concept for this strategy.
I am currently optimising these systems with computational protein design to improve the deliverability of the live biotherapeutic platform which were only recently enabled by breakthroughs in synthetic biology and microbiome research.
To advance my skills and learn from the best in the field, I joined IPD under the mentorship of Dr Gaurav Bhardwaj and Prof David Baker (2024 Nobel laureate).
Here, I have contributed to cutting-edge projects such as developing cyclic peptides for drug synthesis and modular high-efficiency photosynthetic systems. These innovations hold promise for peptide therapeutics, enhanced photosynthetic light reactions and applications in food production or renewable solar fuels.
Working and learning alongside extremely talented researchers including Stephen Rettie, Nathan Ennist, Gizem Gokce, Eric Sun and Jihun Jeung has been an invaluable experience.
In your opinion, why is your research important?
In my opinion, all research holds value and impact, though its relevance may vary depending on the application, audience or timing.
My research lies at the intersection of molecular biology and structural biology, fields that are currently being transformed by the unprecedented capabilities of artificial intelligence (AI) and data science. These advancements have accelerated progress to levels previously unimaginable – tasks that once required an entire five-year PhD project can now be accomplished in weeks.
The capability of creating proteins tailored to specific problems is transforming fields ranging from medicine to renewable energy by enabling us to design molecular solutions with precision and efficiency that were previously unimaginable. It’s an exciting time to be working in this field, where the possibilities for impact feel limitless. This has the potential to address challenges across medicine, agriculture and sustainability.
What inspired you to become a researcher?
Growing up in Honduras, a country blessed with extraordinary biodiversity, I was fortunate to experience the wonders of nature first-hand. From a young age, I was curious and empathetic toward the plants, animals and ecosystems that surrounded me, sparking a deep desire to understand and protect how nature works. These early experiences shaped my fascination with biology.
As I grew older, Honduras faced severe societal challenges, including corruption and instability, which often made society feel illogical and chaotic. Science and nature became my refuge – a place where logic, order and sense prevailed. This connection was further fuelled by inspiring science communicators like Carl Sagan and even movies like Jurassic Park, which introduced me to concepts such as DNA and molecular biology. This made me incredibly curious and since then I have wanted to understand the workings of DNA, evolution and life inside a cell.
In Honduras, this dream felt distant, almost alien – something far beyond my reality. I was often discouraged and told that it was unrealistic. I was fortunate to have a very supportive family with strong women role models who fostered my aspirations. Despite living in a society with sexist views of women’s roles at the time, my mother raised my siblings and I as equals, encouraging us all to dream big and pursue any path we desired. Both my parents and grandparents instilled in me the belief that no goal was out of reach, no matter how impossible it seemed.
What are some of the biggest challenges or misconceptions you face as a researcher in your field?
The biggest challenges I’ve faced as a researcher come from the huge gap between countries like Honduras and research-intensive countries like Ireland. In Honduras, there was no molecular biology programme, no scholarships and very few opportunities to develop a career in science. I had to rely on international programmes, competing with people from countries with far more resources.
Despite my passion and efforts – volunteering for years to learn molecular biology, starting the first molecular biology class at my university, publishing research in collaboration with Radboud University in the Netherlands, and attending international short courses – I was often rejected because I didn’t meet the ‘tick-box’ requirements for coursework. With no feedback on applications or access to scholarship-writing support, I spent more than five years refining my applications and improving my qualifications.
Part of this challenge is how research outputs are valued in determining a researcher’s career. It’s much easier to publish and achieve when you have access to funding, technology and support, which isn’t the case for everyone. This creates an unfair comparison and overlooks the effort and creativity it takes to work with limited resources.
Finally, after countless rejections, I was accepted into the MSc in molecular cell biology and bioinnovation at UCC. This was only possible because Dr Kellie Dean, the programme director, chose to look beyond my lack of formal qualifications and conduct an interview. She recognised my passion and dedication to science and gave me a chance that changed the course of my life. I owe my career to her belief in me.
I graduated top of the class and secured an Irish Research Council scholarship to pursue my PhD with Prof Mark Tangney (who has been an incredible support), at the Cancer Research lab.
There’s a misconception that pure science isn’t important in countries with immediate societal challenges. But I believe that investing in basic science is critical for long-term progress, no matter where you’re from. These challenges have taught me that talent exists everywhere – it’s opportunities and access that are unevenly distributed, and sometimes science and academia are missing out on people who could make impactful contributions due to our culture which encourages privilege.
Don’t miss out on the knowledge you need to succeed. Sign up for the Daily Brief, Silicon Republic’s digest of need-to-know sci-tech news.
