Senior Scientist I/II, In Vitro Pharmacology

The posting, as Gordian Biotechnology wrote it

Are you ready to turn novel, in vivo-validated targets into small molecule drug programs — building the assays, screening cascades and human-relevant models that decide which chemistry moves forward?

Gordian is the leader in applying in vivo screening for target discovery. Our screens are producing novel targets faster than traditional discovery can, but those targets only become medicines if we can drug them, and in vitro pharmacology is where that starts. As our Senior Scientist, In Vitro Pharmacology, you will build assays for targets no one has drugged before, own the screening cascades our medicinal chemists design against, and set the standard for in vitro data at Gordian.
Journey + Destination:

Gordian Biotechnology is a therapeutics company designed as a machine that systematically
reveals the right way to cure age-related diseases: a machine for creating time.

To do that, we built Mosaic Screening, which makes causal validation both grounded in human
pathophysiology and radically more scalable in living diseased tissue. It lets us measure the causal effects of hundreds of perturbations directly in vivo, which reveals therapeutic maxima across vast target spaces (more details on our website and in our preprint ). The machine is already producing wins: across six disease areas, we have mapped nearly as many targets as the field reported in 20 years , advanced a novel osteoarthritis candidate into IND-enabling studies, and started an obesity drug-discovery collaboration with Pfizer.

But there are still many diseases left to cure, and expanding the machine to tackle them starts with its most important resource: its people and culture. We work as a team , using clear goals, open communication, and direct feedback to make autonomous decisions with the bigger picture in mind. We aim for extraordinary outcomes , continually improving how we work and acting on what will create the most progress, even in unknown territory. We have deliberately designed an environment to sustain that standard: few standing meetings, hands-on experimentation and pre-mortems, weekly team lunches, and unlimited vacation that people are encouraged to use. You can dive deeper into our culture here .

This way of working has been crucial to Gordian’s success. In this role, you will help turn the targets the machine produces into small molecule medicines.

The Role

Your mission is to make three things work across our obesity, kidney (CKD/DKD) and heart failure (HFpEF) programs:

• Assays for novel targets. Most of our targets have no tool compounds, no off-the-shelf assay and incomplete pathway biology. You will design, develop and validate the biochemical, biophysical and cell-based assays that let us find and optimize chemical matter against them.
• The screening cascade. Through working with our medicinal chemists, you will design the cascade from hit identification through lead optimization — primary, orthogonal, counter-screen, selectivity, functional and

[…]
have designed or owned a screening cascade from hit identification through lead optimization or candidate nomination, partnering with medicinal chemists on SAR, and your experience includes cardiometabolic, renal or cardiovascular drug discovery.

You build assays for targets no one has drugged before. You have developed assays from scratch for poorly characterized targets with no tool compounds or established readouts, across target classes such as GPCRs, enzymes, nuclear receptors and transporters.

You have scoped and managed CRO studies, transferred assays with bridging data, and caught and corrected external data-quality problems. You analyze data rigorously (e.g., GraphPad, Genedata, Spotfire; Python or R a plus) and document your work so others can find, reproduce and build on it.

You communicate so that decisions follow. You can explain what an assay measures, and what it does not, to chemists, biologists and executives, and you bring a clear recommendation rather than a data dump.
Additional valuable skills if you have them

• Experience across more than one of kidney, cardiac and metabolic biology.
• Target engagement and biophysical methods such as CETSA, NanoBRET or SPR.
• First-in-class target experience, with no prior chemistry or tool compounds.
• Lab automation, liquid handling or high-content imaging.
• Advanced human cell models: iPSC-derived cells, 3D cultures or organoids, engineered heart tissue, kidney organoids or microphysiological systems.
• Understanding of PK/PD and in vitro to in vivo translation in cardio-renal disease.
• Partner- or BD-facing experience presenting preclinical data.

The Details

This is an onsite role in South San Francisco because hands-on lab work is central to it. Gordian offers meaningful equity, a competitive salary, full health, dental, vision, and life insurance, a 401(k) with match, onsite lunch three days a week, an onsite gym, an unlimited vacation policy, and access to world-class mentors and advisors.