Principal Scientist, Biophysics

Full-time, hybrid role based in Boston, MA

At HotSpot, we’re not just looking for the brightest minds or for the most brilliant individual contributors. We want passionate team members who are comfortable adjusting their lens, aren’t afraid to think big, test bold ideas, and celebrate collective wins. We have established core values that resemble who we are and define our company culture. We are building a company where values drive everything we do inside and outside the organization. #Courageous Adventurers #Leave your Mark #Keep it Human #Make it Real 


  • Effectively interact with colleagues in biochemistry, cell and chemical biology, computational and medicinal chemistry, plus other functional groups, to apply biophysical tools to solve project specific problems driving project progression
  • Design a biophysical strategy for characterizing the molecular interactions of our small molecules with the allosteric site on the target proteins in the form of monomer or high order complexes.
  • Proficiently use a wide range of biophysical methods such as SPR, MST/Dianthus, Nano-DSF, SEC-MALS, TSA, etc., to characterize target proteins and interactomes.
  • Contribute to the recombinant protein design, protein expression, and protein purification, for biophysical assay development and validation.
  • Manage the biophysics lab in house, including at least 50% of the time working at the bench, supervise other scientists at the bench, maintain the instruments in the biophysical lab, provide guidance for trouble shooting and ensure the timely delivery of the high-quality data to the projects.
  • Manage external CROs. Balance the internal and external resources to meet the quality and through put requirement of the projects. Efficiently accomplish project goals on time and within the budget.
  • Stay scientifically current, and willingness to implement new technologies to the biophysical assays focusing on allosteric binding sites
  • Make intellectual contributions to all stages of drug discovery process and project deliverables.  Clearly articulate goals, progress, and issues to drug discovery teams.


  •  Ph.D. degree in biophysics, biochemistry, or related discipline, with 7+ years industry experience in small-molecule drug discovery
  • Proven track record of developing and implementing biophysical assays to support drug discovery using a variety of detection formats. Experience with allosteric binding sites on proteins is a plus.
  • Extensive industrial experience in biophysical and biochemical assay development, especially SPR and MST/Dianthus, but preferably also one or more of Nano-DSF, SEC-MALS, TSA, Cryo-EM, X-ray crystallography, ITC, NMR, TR-FRET, AlphaLISA, etc.
  • Experience balancing CRO and internal resources to solve problems and drive progress
  • Exceptional interpersonal and communication skills, and ability to work seamlessly with multiple drug discovery teams to provide biophysics supports at all stages of the project
  • Excellent organization and management skills, including the ability to set high but reachable goals, ability to manage multiple projects and capability to prioritize
  • Strong interpersonal, influencing and collaboration skills to work in a team-oriented, matrix environment, and the ability to work independently and effectively within tight timelines
  • Outstanding verbal and written communication abilities with a strong publication record
  • 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


We believe that people are our greatest resource and foster a supportive environment that provides growth and development for all teammates. We recognize and reward performance and incentivizes long-term success. From benefits that focus on your health and well-being to competitive compensation to ownership in the company, we want to inspire our employees.

Our Benefits Include, But Are Not Limited To:

  • Competitive salary and bonus plans
  • New hire stock option award
  • Comprehensive package of benefits plans and fringe benefits
  • Generous paid holidays, time off, including 2 company wide shutdowns
  • Flexible working arrangements; hybrid work model
  • Amazing team of supportive colleagues

At HotSpot, we have a bold mission to establish a new drug discovery paradigm. If this appeals to you, please apply. HotSpot is an equal opportunity employer. We celebrate diversity and are committed to creating an inclusive environment for all employees.

HotSpot requires its employees to be fully vaccinated against COVID-19, as defined by the CDC. Additionally, HotSpot employees are required to comply with state, local, and vendor COVID-19 vaccination requirements.

Apply today!
[email protected]