Within every human cell, nature has engineered finely tuned control mechanisms to correct imbalances caused by stress and disease and promote healing. At HotSpot Therapeutics, nature is inspiring us to create a wave of new medicines.
Through a proprietary technology platform, we are uncovering privileged allosteric sites used by nature to control proteins – called natural hotspots- that can be exploited through small molecule drug discovery. Natural hotspots are allowing sought-after targets to be drugged for the first time while delivering molecules with exquisite selectivity and attractive drug-like properties.
HotSpot is supported by a syndicate of leading healthcare investors based in the US and Europe. You will be joining a seasoned team of drug hunters with an excellent track record in drug discovery. As a HotSpotter, you are comfortable thinking outside the box and breaking convention. You are curious about the world and contribute beyond your precise role description. You are action oriented and extraordinary at getting things done. You communicate openly with your colleagues, and you hate office politics.
We are seeking an experienced, highly skilled structural biologist to join a high-performance biochemistry and biophysics team at Hotspot therapeutics. The successful candidate will provide vision for the structural biology function and be involved in all aspects of structural biology to impact discovery of novel medicines in oncology and inflammatory diseases. The primary technical responsibilities are protein engineering, protein production, solving structures of small molecule with target proteins, and work collaboratively with chemistry and computational chemistry team to support rationale-design SBDD.
- Lead the scientific, technical, and operational aspects of structural biology for drug discovery programs
- Lead a multitude of efforts in parallel including X-ray, NMR, and Cryo-EM; each with a clear goal of delivering novel and iterative protein structure with small molecules to enable structure-based drug design.
- Design structural biology strategies, protein engineering using rational design, fusion proteins, loop deletions, surface entropy reduction, and mutagenesis
- Build a world class protein sciences team, supervise the design of protein constructs and protein production to support the assay development
- Effectively interact with colleagues in biochemistry and biophysics, computational chemistry, medicinal chemistry, cell biology, and other functional groups to drive project progression
- Manage external resources to ensure delivery of high-quality protein structural information, efficient recombinant protein design, protein expression, protein purification, crystallization, data collection, and refinement
- Devise and implement experiments to develop robust protocols to generate iterative co-complex structures, perform structural refinement with in-depth understanding of drug-protein interactions and articulate clearly detailed findings to the team
- Demonstrated track record of accomplishments through use of strong problem-solving skills
- Lead structure biology aspect of publication and poster presentations
- Ph.D. degree in structural biology or related discipline with at least 10 years of industry experience
- Proven ability to design and troubleshoot constructs for crystallization, solve structures for technically challenging proteins, and co-complex of small molecules with target proteins
- Extensive experience in solving protein structures using X-ray crystallography, cryo-EM and NMR
- Demonstrated track record of success in structure-enabled drug discovery programs, as evidenced by a significant publication record in journals, patents and presentations
- Experience in using analytical/biophysical techniques (SEC-MALS, DLS, DSF, etc.) for assessing stability, solubility, and oligomerization status of proteins
- Experience in managing CROs to solve problems and drive progress of the projects
- Exceptional interpersonal and communication skills, and the ability to work seamlessly with multiple drug discovery teams and provide structure related support at all stages of the project
- Strong organizational skills, ability to manage multiple projects simultaneously, and the capability to prioritize and focus on delivery of data for key decision making
- Efficient and comfortable with working remotely with teams at different locations
- Ability and willingness to learn and adopt emerging technologies to drug discovery process
- Ability to adapt to and effectively manage changes in a fast paced, dynamic environment
- A passion for drug discovery and sense of urgency to find new medicines for patients
HotSpot is an equal opportunity employer. We celebrate diversity and are committed to creating an inclusive environment for all employees.