Exploring Biotech Frontiers: Synapsis by Dojo's Inaugural Edition
Celebrating Milestones, Insights, and Innovations in Biotechnology
Welcome to the inaugural edition of Synapsis by Dojo, where we celebrate milestones, explore cutting-edge biotech insights, delve into personal scientific journeys, and highlight transformative initiatives shaping the industry. In this issue, we spotlight Dojo's dynamic growth through initiatives like DojoExplore and DojoHouse, showcase pioneering gene therapy innovations, delve into the subjective pathways driving scientific discovery, and introduce opportunities in biotech through collaborations like MITx and Entrepreneur First. Join us as we embark on a journey through the vibrant world of biotechnology, where curiosity meets innovation to redefine the future of healthcare and beyond.
Dojo Dynamics: Celebrating Our Achievements and Looking Ahead
DojoExplore Unveiled:
Our DojoExplore initiative launched a 5-week introductory to biotech seminar series at UC Berkeley and McGill University, featuring guests ranging from biotech VC to early-stage biotech founders to industry and academia leaders, and engaging discussions to foster vibrant biotech communities on campus. We’re thrilled to expand Explore to more campuses this fall!
At McGill, the program welcomed over 80 participants with brilliant speakers from the Montreal area and concluded with a lively mixer. Moving forward, a newly recruited team is preparing to bring more exciting events to Montreal on a regular basis. At Berkeley, we invited speakers from some of the Bay Area’s leading biotech startups such as Mammoth Biosciences and LatchBio, providing many invaluable insights into the biotech ecosystem. Looking ahead, we plan to introduce DojoExplore at the University of Toronto, University of Connecticut, University of British Columbia, University College London, and possibly more.
Across the pond in London, our mixer was a melting pot of ideas and opportunities. DeSci London looks forward to collaborating through their Muse Matrix fellowship, connecting networks with Boston and Canada. We’re also exploring partnerships with the Long Bio fellowship in London and the KCL iGEM team, while DojoHouse London is gaining attention from venture capitalists and EF representatives.
DojoHouse Updates:
This summer, Dojo House was back, offering ambitious undergraduate students in biotech the opportunity of free housing in Boston and San Francisco. Supported by Emergent Ventures, Amaranth Foundation, TIME Initiative, and 1517, this program promised immersive experiences where participants engaged with industry founders over dinners, visited cutting-edge startups and academic labs, and networked within the vibrant biotech community. For more details about the program and to meet this year's cohort, check out the full article.
Community Engagement and Initiatives:
Synapsis by Dojo is here, marking a new beginning. Be on the lookout for similar articles every month. We've refreshed our Discord community and are creating more educational resources for undergrads.
As we move forward, community engagement remains central to our mission. Explore our server's new look and join the lively discussions that define our community. We invite you to connect with fellow members, share ideas, and contribute to the vibrant conversations happening on Discord. Your participation helps strengthen our network and fosters a supportive environment for all.
Sponsorship Success:
A big thank you to the sponsorships team, who have been working tirelessly behind the scenes. From sending countless cold emails to making connections, helping different programs strategize and fundraise, and figuring out the best way to position Dojo within biotech key players—their energy has been instrumental. Thanks to their efforts, we secured significant funding this year, and we're just getting started!
Nucleate Alumni Summit Recap:
Last month, Dojo leadership and alumni from Dojo House in San Francisco attended the Nucleate Alumni Summit at 1440 Multiversity in Santa Cruz. This event served as a dynamic fusion of ideas and inspiration, bringing together colleagues from around the globe. The summit featured insightful talks on topics such as the future of AI, bridging academia and industry through entrepreneurship, addressing unmet healthcare needs with technology, and exploring diverse career paths in biotech.
The summit provided an excellent opportunity to connect with remarkable scientists, founders, and like-minded individuals, broadening networks and enhancing understanding of the field's direction. Key discussions underscored the importance of bio literacy, the value of building meaningful connections, and the necessity of resilience in this rapidly evolving industry. For undergraduate students interested in biotech, connecting with Nucleate Dojo and considering attendance at next year's summit is highly recommended, as it promises to be an enriching experience that opens up new possibilities and insights.
A Heartfelt Farewell to the 2023-2024 Leadership Team:
As we bid farewell to the remarkable 2023-2024 Dojo leadership team, we extend our heartfelt gratitude for their incredible contributions and achievements over the past year. This outstanding group of individuals has worked tirelessly to advance our mission, creating lasting impacts within the biotech community. While some members will continue their journey with us, others are embarking on new chapters in their lives, and we wish them all the best. Stay tuned for the announcement of our 2024-2025 leadership team, as we prepare for another exciting year filled with opportunities and growth!
Looking back on our progress and looking forward to future milestones, Dojo leads in innovation and collaboration. Together, we're on a journey driven by curiosity, passion, and a shared vision for a better future. Join us as we explore, learn, and grow together, using community power to shape the biotech world of tomorrow.
Biotech Insights: Innovations in Gene Therapy
While many may think of RNA therapeutics and CRISPR when thinking about gene therapy, the oldest and probably most studied method for gene therapy is gene addition/augmentation therapy (GAT). In such therapies, a transgene is introduced into patient cells, enabling expression of a protein - perhaps one that kills the cell itself (such as in suicide gene therapies for cancer), or that restores levels of activity for a protein that the patient is lacking. The latter comes with some obvious limits on which kind of conditions it can treat - the diseased allele is not being corrected and its product is not being removed, so only a loss-of-function mutation can be tackled. However, one slightly less obvious drawback is the difficulty associated with achieving precise levels of expression. Thus, previous successes in GAT have involved genes that did not require such tightly regulated levels. As one can imagine, relatively few conditions meet this requirement. For example, beta-thalassemia, which was originally thought to be a promising target for gene therapy due to its small coding region and easily accessible target tissue, turns out to have complex regulatory requirements, with respect to both cell type specificity and balance with alpha-globin levels. One way to overcome this limitation is exemplified by the recently approved CRISPR/Cas9 drug CASGEVY, which circumvents the problem and instead increases the expression levels of foetal haemoglobin. Another way to tackle the issue is proposed in a recent preprint by the Elowitz group at Caltech, which we will explore in this section.
First, let us look at Rett syndrome, the condition that this new method is applied to in this preprint. It is a neurodevelopmental disorder caused by loss of function mutations in MECP2, which is key to silencing methylated regions of the genome. Disease phenotypes are also caused by mild overexpression and gene duplication of MECP2. As an X-linked condition, Rett syndrome has an added level of complexity. Due to random X inactivation - where all cells in females have one of their two X chromosomes silenced - females heterozygous for the MECP2 mutation will have some cells expressing no MECP2, while others will express one copy. Thus, the background level which the transgene is adding to varies, and this also needs to be compensated for in order to achieve levels that fall within the narrow window for a non disease phenotype.
Gene dosage compensation
There is a large variability in uptake by different cell types, and also individual cells of any given type. This leads to each cell having a different copy number and so some may be underdosed and some overdosed. The proposed solution is to include a negative regulator that is co-transcribed with the target gene, meaning that high copy numbers also result in higher levels of negative regulation, thus maintaining a constant level. In this case, the negative regulator was an miRNA cassette, placed in a synthetic intron in the 3’UTR of the transgene.
Promising results in a mouse model
Using the brain-specific targeting delivery method, AAV-CAP.B22, the success of this method was tested in mice. To look at the strength of regulation needed, they used three constructs - one completely unregulated, one with 1 miRNA target site, and one with 4 sites.
Efficacy was quantified using standardised Rett phenotype scores, which account for various motor traits. The mice treated with the construct containing 4 sites showed much lower scores, and lower standard deviations, than the untreated mice or those with less regulated constructs.
This technology provides an exciting avenue for achieving consistent expression of transgenes in gene addition therapies, without the need to fit the often bulky gene regulatory regions into size-limited delivery vectors.
Full paper (along with the figures included in this essay) available at: https://www.biorxiv.org/content/10.1101/2024.03.13.584179v1.full
Subjective Pathways: How Personal Experiences Drive Scientific Discovery
By Mukundh Murthy
It’s interesting to think about the variables that drive scientific research forward, the moments during a scientist's journey that define the transition between a series of long iterative experiments to a defining translational or theoretical insight. While science seems inherently “objective,” there’s such a large number of potential insights about the natural world to discover, and a multitude of paths to discover each insight. In that sense, the practice of science could be seen as subjectively guided; each person’s unique life experiences and upbringings can guide the questions they investigate and the way they approach those questions.
For example, Einstein developed his theory of relativity through numerous thought experiments, which are a way to think about a scientific concept in a way that’s analogous to a real-world situation you’ve experienced before. Geoffrey Hinton invented the concept of dropout in neural networks – the idea that neural networks can achieve better overall performance on data that they haven’t seen before by probabilistically removing random subsets of neurons during training – during his visit to a bank:
“I went to my bank. The tellers kept changing and I asked one of them why. He said he didn’t know but they got moved around a lot. I figured it must be because it would require cooperation between employees to successfully defraud the bank. This made me realize that randomly removing a different subset of neurons on each example would prevent conspiracies and thus reduce overfitting.” — Geoffrey Hinton
Humans can often understand and develop progress in science by making analogies between real world situations and their mental models of how the world works, and the mental models are further developed by extending aspects of those analogies.
Implications of a critical realism approach to chemistry research and education is a commentary article from nature that discusses this concept of how subjective experiences drive the discovery of the objective through experience-driven mental models and analogies. We observe the “Empirical” – actual events that can be observed in the real world and then use models to infer unobserved mechanisms that can explain what we see.
This methodological approach to understanding what drives scientific epiphanies and progress gives another answer as to why diversity is so important in order to drive science forward. Diversity enables us as a human collective to sample from so many potential world models (fueled by diverse experiences and perceptions), thereby enlarging the pool of hypothetical unobserved mechanisms that can explain a given phenomena and enabling more robust, objective science in the longer term.
Dojo Database
Entrepreneur First
Entrepreneur First, who collaborated with us to host our first event in the UK, invests in talented individuals and gives them the network and guidance they need to thrive in the start-up space. If you’re an undergraduate student or graduated less than two years ago, their Graduate programme may be for you! Your application is assessed based on your potential as an individual - you don’t need to have a concrete idea, just a passion for building something new and a desire to work hard to make it happen. Examples of biotech companies that have come out of this programme are Ochre Bio
The programme is split into two twelve week stages, Form and Launch. During the Form stage, you’ll have the opportunity to develop an idea, while also getting to know your cohort and find someone whose passions align with yours. After this, you will pitch for pre-seed funding at their Investment Committee, and the top few teams will progress to the Launch stage. This phase will facilitate further expansion of your startup idea, with the chance to relocate to San Francisco and become part of the vast startup community there. The programme culminates in a demo day, pitching to investors in Silicon valley and across the world.
Visit https://apply.joinef.com/ to find the application deadlines for the location you are interested in - applications are still reviewed once they are “closed”, so don’t hesitate to register your interest and get involved in this exciting accelerator.
Discover Your Path in Biotechnology with MITx
Curious about biotechnology and how you can make a mark in this exciting field? The course MITx: The Science and Business of Biotechnology is designed to guide you through the complexities of biotechnology and help you find your niche.
Over 16 weeks, with a commitment of 10-12 hours per week, this self-paced course delves into the latest scientific innovations and explores novel business and financing models for commercializing biotechnology. You'll learn about recombinant therapeutic proteins, monoclonal antibodies, cancer immunotherapies, gene therapies, and more. The course also covers financial techniques to reduce risks and bring life-saving therapies to patients faster.
Designed for life-sciences professionals, the course is taught by esteemed instructors, including Professor Andrew W. Lo, Professor Harvey F. Lodish, and PhD student Zied Ben Chaouch.
Note: Due to U.S. sanctions, learners from Iran, Cuba, and the Crimea region of Ukraine cannot register for this course.
For more information and to access the course materials, visit the MITx course page.
The Biotech Startups Podcast
If you’re a student curious about the world of biotech and the entrepreneurial journey, check out The Biotech Startups Podcast hosted by Jon Chee, and brought to you by Excedr. Each week, the podcast features discussions with various leaders in the life sciences, including scientists, founders, and investors, who share their experiences and insights.
This podcast offers a closer look at the realities of running a biotech startup, highlighting both the challenges and successes in the industry. It’s a great resource for anyone interested in how science and business intersect, providing inspiration and practical knowledge for those considering a path in biotech or entrepreneurship. You can listen on platforms like Apple Podcasts, Spotify, or YouTube to learn more about the dynamic field of biotechnology.
A Bright Future for Dojo
As we wrap up this inaugural edition of Synapsis by Dojo, we reflect on the remarkable progress made within our community and the exciting journey that lies ahead. The fusion of diverse ideas, innovative research, and collaborative spirit drives us to explore the vast possibilities in biotechnology. With continued engagement and a commitment to learning, we invite you to join us in shaping the future of this dynamic field. Together, we can harness the power of our collective experiences and insights to inspire change, foster discovery, and pave the way for the next generation of biotech trailblazers. Stay connected with us as we share more stories, resources, and opportunities in our upcoming editions!