December 2022 Progress Update
(Calendar) Year in Review
This month, we’re reflecting not only on our progress for the past 30 days, but also our progress during the calendar year.
(Calendar) Year in Review
NewLimit began operations in March of 2022. We began with only two full time employees and no functioning labs. NewLimit had never run an experiment or trained a model. Our roadmap branched in many directions, and we hadn’t yet crystallized on our first product directions.
In the past nine months, we recruited a remarkable team of scientists and engineers spanning genomics, immunology, and machine learning. Our full time headcount now stands at twelve, and we no longer fit around a single kitchen island for lunch each day.
In June, we found a physical home in South San Francisco, CA fit for our growth in coming years. Our Operations team rapidly transformed the empty shell into a world-class functional genomics lab.
Beginning in the last week of September, we ran our first experiments. It all started with a restriction digest, the very same reaction that birthed the biotech industry nearly 50 years ago. From there, it was off to the races.
Before year’s end, we ran a partial reprogramming screen with more diverse perturbations than ever before, generated large-scale epigenetic maps of immunosenescence, and implemented a next-generation single cell profiling chemistry. In the world of bits, we trained our first cell function prediction models and built out the infrastructure to analyze our first reprogramming screens. Each week now yields more data than the weeks before, reminiscent of the transition to log-phase growth in a cell culture.
We couldn’t be more proud of the progress our team has made toward making reprogramming medicines a reality. Each of our accomplishments is a testament to their talent and hard work. Looking forward to 2023, we’re excited to assemble the newly forged pieces of our Discovery Engine and begin the development of our first therapeutics.
Progress
Operations
Expanding our team
We welcomed two new team members in the month of December!
We’re excited for the first Research Associate to join our Epigenetic Editing team and the first Principal Scientist to join our Single Cell Technology team in the coming months.
New robots in the lab
We added our first fully-automated flow cytometer to accelerate our immunoprofiling experiments. All of us are excited to transition more of our experimental work to diligent, indefatigable robots in the coming year.
Atoms
Pooled reprogramming chemistry demonstration
We designed a pooled reprogramming system in September and October 2022, and this month the very first sequencing reads using our chemistry arrived in a NewLimit cloud bucket. We never tire of seeing basepairs we assembled with our own hands — never before found in nature — appearing on our terminals.
…TGGGAAGTCTCTTGTACG…While the libraries from our first screen are being sequenced, we spent the last weeks of December running quality control analyses on these initial demonstration data. We found our chemistry allowed for reliable detection of reprogramming perturbations in >90% of profiled cells, enabling pooled combinatorial experiments.
Expanding our palette of reprogramming chemistries
We’ve been building two additional pooled reprogramming chemistries in the background, and our experiments in this regard kicked into high gear at the end of December.
One of these new chemistries is focused on increasing the scale of our screens by making reprogramming libraries easier to manufacture. We’re optimistic that we can repeat our success from November 2022 and achieve another 10X improvement.
The other chemistry we’re actively developing uses an entirely different molecular system to perform reprogramming. This system allows us to test a more diverse set of reprogramming factors in our screens, but sacrifices control of other variables.
We hope that using each of these chemistries in parallel will allow us to discover more than we could with any one alone.
Completing maps, finishing screens
In November 2022, we began building an epigenetic map of aging in human T cells using functional genomics methods. This month, we completed our first round of experiments and sent off an initial set of libraries for sequencing.
We likewise initiated our first partial reprogramming screen at the end of November. This month, we completed the experiment and sent off our first libraries for sequencing. We look forward to having these base pairs in cloud buckets soon.
Bits
Turning basecalls into biology
As our first in-house sequencing data flowed in, we spent the last few weeks of December implementing bioinformatics workflows to turn those raw base calls into biological insights.
We’re privileged to stand on the shoulders of giants in this regard, and we’ve adopted a rich suite of classical bioinformatics and machine learning tools that enable us to extract as much information as possible from each of our single cell genomics experiments.
These workflows will allow us to automate a large fraction of the traditional computational biology tasks, allowing our servers to focus on aligning reads while our scientists and engineers focus on interpreting results and learning representations of our biological system.