June 10, 2024 | Read Online​

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Good morning, pioneers!

Here’s what we’ve got for you in this month’s email:

• ​The key to moving the 3D culture industry forward​
• ​Open-source resources to master 3D cell culture​
• ​2 must-attend events for pioneers in 3D biology​

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Let’s get into it 🧬!

KEY OPINION LEADERS

Advancing 3D Culture & The Need for Knowledge Sharing

This month, we sat down with Dr. Maryna Panamarova, a technical expert in the 3D culture space. Dr. Panamarova is working to develop and upscale novel organoid models at the Wellcome Sanger Institute. She is an advocate for making knowledge open source and believes it’s key to advancing the industry forward.

Dr. Panamarova’s journey into scientific research began in 2007 during her undergraduate years at the University of Edinburgh where she landed an internship at the Centre for Regenerative Medicine.

Induced pluripotent stem cell technology was starting to emerge, and she had the chance to work with human embryonic stem cells alongside fantastic mentors who fanned the flames of her interest in regenerative medicine.

Dr. Panamarova pursued a Ph.D. at the University of Cambridge. Together with her Ph.D. mentor, Magdalena Zernicka-Goetz, she showed the effectiveness of using advanced cellular models to investigate complex biological processes, such as cell fate determination. In 2015, Dr. Panamarova took a postdoc position at King’s College London, where she focused on finding new treatments for incurable muscular dystrophy (FSHD) using advanced 3D models.

Today, Dr. Panamarova continues to lead cutting-edge research in the 3D model space. She works as a Cellular Modelling Research Specialist at the Wellcome Sanger Institute in the UK in their Scientific Operations team.

Making leaps in understanding human diseases using 3D models

Where are you with your work right now? What's your focus at the moment?

Dr. Panamarova: I work within the Scientific Operations team at the Wellcome Sanger Institute. The Sanger Institute, based in the UK, is a world-leader in genomic research that delivers insights into human, evolutionary, and pathogen biology.

The Scientific Operations department helps deliver science at scale by developing and championing an array of cutting-edge technologies in sequencing, cellular and molecular biology, and spatial genomics.

In the Cellular Modelling team within Scientific Operations, we are focused on large-scale production, biobanking, and validation of advanced cellular models from patient-derived tissues and reprogrammed stem cells.

Over the years, our team has made significant contributions to various global and national initiatives aimed at developing improved models for studying human diseases. Among them are the Human Cancer Model Initiative (HCMI), an international effort to establish patient-derived next-generation cancer models, and IBD Response, a UK-wide study to predict and model patient responses to therapeutics in Inflammatory Bowel Disease.

How have you seen the industry change since you’ve been a part of it?

Dr. Panamarova: I joined Sanger in 2020. Since then, organoid technology has undergone remarkable advancements that broadened our access, understanding, and application of in-vitro models of human biology and disease.

One significant development is the refinement of protocols for organoid generation and culture. There have been advancements in optimising culture conditions, media compositions, and growth factors, leading to more efficient and standardised protocols. At Sanger, our team openly shares the protocols that we use via our protocol.io and YouTube channel. We also collaborate with Wellcome Connecting Science to offer an Advanced Organoid Course designed for experienced researchers seeking to get experimental skills in organoid culture and applications.

There has been a notable increase in the complexity of organoid models. There is currently a big drive to create advanced microphysiological systems (MPS) by incorporating multiple cell types and recapitulating tissue architecture more accurately. This increased complexity enhances the physiological relevance of organoids and allows for more accurate modelling of tissue function and disease pathology.

The surge in interest surrounding organoids has catalysed technological advancements, enabling improvements in throughput and downstream processing. The integration of organoid technology with other state-of-the-art methods, such as single-cell RNA sequencing and CRISPR-Cas9 genome editing, has amplified the potential of organoid models in fundamental research and drug development.

Working in silos slows down our progress with 3D culture

How do we get industry to align and develop a consensus as opposed to working in silos?

Dr. Panamarova: I think a big part of alignment is transparency to a degree.

That extends far beyond individual pharma companies and individual labs or research institutes. It fosters an environment where researchers can share protocols and methodologies and it really strengthens the field.

Within this framework, an institute like Sanger plays an important role. One of our core tenets is that we are championing open access to the data we generate.

We aim to share all of the models that we produce with the scientific community and disseminate the protocols and the data associated with 3D workflows. We try to do as much of that as possible.

Through the repositories, I think the scientific community as a whole can access published models, methods, and expand on existing knowledge.

I just wanted to give you a really good example from our colleagues at EMBL's European Bioinformatics Institute (EMBL-EBI). EMBL-EBI is located at the Wellcome Genome Campus, as is the Sanger Insitute, which creates unparalleled opportunities for information exchange and collaboration, so I know their work really well.

A notable example of an open-source resource is called cancermodels.org. It was developed by EMBL-EBI in collaboration with the Jackson Laboratory. This platform simplifies access to published cancer organoid models from academic and commercial providers. It utilises a standardised approach to all of the data that are published and associated with it.

Because if you are a wet lab scientist and you want to select a tumour model that has a particular phenotype, you need to go through numerous publications, download all of the associated data and compare it with some other models. Usually, it requires a huge time investment and computational skills which not everyone has.

And if you gatekeep it at that level, the field itself will move at a slower pace than it otherwise would.

So, for people who are working with tumour models, I recommend utilising this platform. It's a great example of an open-source resource that's brilliant.

What are some exciting technologies in the 3D space that have caught your eye?

Dr. Panamarova: Microfluidic chips really caught my eye recently. I think they have massive potential to advance complex organic culture techniques.

By leveraging microfluidics, I think organoids can be cultured in an environment that more closely resembles in-vivo conditions than your standard Matrigel dome culture.

That means including something that simulates the blood flow, gradients of nutrients and oxygen, and signaling molecules.

That said, this isn’t something that we've been actively looking into, but from the conferences and meetings that I attend, I certainly keep my eye on that territory.

Fellow pioneers in 3D biology

Are there any specific people or research groups that you look to as fellow pioneers in the space?

Dr. Panamarova: I really like the work that is done at the Swiss Federal Institute of Technology in Lausanne (EPFL). It’s quite new, but still very impressive work coming out of there.

I like it because, similar to Sanger, they not only publish very interesting work, but also put significant emphasis on developing technology behind organoid culture and screening. I always keep a lookout for new ideas that I can bring back.

Are there any conferences that you would recommend that you that you've particularly enjoyed that have had a central focus on in-vitro 3D biology?

Dr. Panamarova: We had a conference back in February at the Wellcome Genome Campus called World Organoid Day, which was really good. And then there was an organ modelling conference in London in March that I went to that was more industry-centered.

There is another organoid conference that's going to be here at the Wellcome Genome campus in September run by Wellcome Connecting Science.

Final thoughts?

Dr. Panamarova: I just wanted to thank you for asking me to contribute my perspective to the newsletter.

It's been wonderful to be involved in the discussion and I'm looking forward to more chances to collaborate and share ideas.

Read Dr. Panamarova’s full interview here.

RESOURCES

3D Resources from The Wellcome Sanger Institute