Many of our rotation graduate students and potential undergraduate researchers ask us what the difference is between ” chemical biology” and “biochemistry.” There is a great Venn diagram here, with much shared overlap. And we do both in our lab…though we prefer the chemical biology side of the Venn.
These two fields share significant overlap, and many people tend to use the terms interchangeably in ways that don’t help. But seeing both sides will help you choose a lab that fits best for you!
Here’s a clear breakdown.
Our Short Answer
Biochemistry asks: what are the molecules in living systems, and how do they function?
Chemical biology asks: how can we design new chemical tools to probe, control, or modify those molecules — and what does that tell us about disease?
Biochemistry tends to work with the molecules biology gives us. Chemical biology builds new molecules and biomolecules (which we call “probes”) to ask questions that existing, natural systems can’t answer.
What Biochemistry Studies
Biochemistry is the study of the chemical processes that occur in living organisms. It focuses on understanding naturally occurring molecules — proteins, nucleic acids, lipids, carbohydrates — and the reactions they participate in.
A biochemist might characterize the kinetics of an enzyme, map a metabolic pathway, or identify how a mutation alters protein folding. The orientation is largely descriptive and mechanistic: here is how this system works.
Biochemistry sits firmly within biology departments at most universities, though it shares methods with molecular biology, cell biology, and structural biology. The questions tend to start with the organism and move toward the molecule.
What Chemical Biology Does Differently
Chemical biology starts from a different position. Rather than observing biology as it exists, chemical biologists design synthetic tools — small molecules, probes, modified substrates, and engineered proteins or nucleic acids — to interrogate biological systems in ways that natural molecules and biomolecules (protein, DNA, RNA) cannot.
The orientation is intentionally to perturb a system to learn from it. We build something new, introduce it into a biological context, and use its behavior to reveal something about the system that would otherwise stay hidden!
Chemical biology approaches are particularly powerful for studying processes that are hard to observe directly. Protein glycosylation is a perfect example. The addition of sugar molecules to proteins (O-GlcNAc modification, for instance) plays a significant role in how cells respond to metabolic stress, yet studying it with conventional biochemical tools is technically difficult. Also, glycans and O-GlcNAc are NOT genetically encoded the way the RNA and proteins are, so they are much more difficult to predict (although machine learning helps us).
Chemical biologists design probes that can tag, track, or block specific glycosylation events to understand what those events actually do in cancer, diabetes, and neurodegeneration.
How the Tools Differ
| Biochemistry | Chemical Biology |
|---|---|
| Purified proteins and natural substrates | Synthetic probes, modified substrates, chemical reporters |
| Genetic knockouts and overexpression | Small molecule inhibitors, activity-based probes |
| Spectroscopy, gel electrophoresis, ELISA | Click chemistry, bioorthogonal labeling, fluorescent reporters |
| Observing natural systems | Engineering access to specific biological events |
Both fields use mass spectrometry, cell-based assays, and structural techniques. The difference is less about the instruments and more about the starting question and the tools designed to answer it.
Where They Overlap
The boundary between biochemistry and chemical biology is quite open. Many research groups use both approaches, and the best chemical biology work is grounded in solid biochemical understanding.
Biochemistry informs chemical biology by defining which pathways and proteins matter. Chemical biology returns the favor by generating tools that make biochemical questions answerable at higher resolution or in more physiologically relevant contexts.
Molecular biology overlaps with both, particularly around gene expression and nucleic acid function. Pharmacology shares chemical biology’s interest in small molecules but focuses more on therapeutic application than on tool development for basic research.
Also, we tend to validate the observations we make with our chemical biology tools in a natural, wild-type, biochemical system in order to make sure we did not introduce a chemical artifact into our biological finding. So…we end up doing both types of experiments anyway!
What This Looks Like in Metabolic Disease Research
At the Fehl Lab at Wayne State University’s Department of Chemistry, we work primarily in chemical biology. We design chemical tools to study carbohydrate-linked proteins and the glycobiology pathways connected to cancer, diabetes, obesity, and neurodegeneration.
We combine those tools with machine learning to identify patterns in glycobiology data that would be difficult to detect otherwise. That combination — custom chemical tools plus computational analysis — lets us ask precise questions about how sugar modifications on proteins drive metabolic disease.
This is exactly the kind of work that sits outside the scope of traditional biochemistry. We’re not just characterizing what exists; we’re building the instruments to see what’s been invisible.
If you’re a new graduate student, potential undergraduate researcher, or early-career researcher thinking about which direction to pursue, chemical biology is worth serious consideration if you’re drawn to building things, working at the chemistry-biology interface, and connecting molecular-level work directly to human disease outcomes.
Learn more about our research and current projects at fehl-lab.com.
Which Field Is Right for You?
Consider biochemistry if you:
- Want to deeply understand how natural biological systems work
- Prefer mechanistic, systems-level questions
- Are drawn to structural biology, enzymology, or metabolomics
Consider chemical biology if you:
- Want to design tools to probe biology, not just observe it
- Are comfortable working across chemistry and biology
- Want your research to connect directly to disease intervention and drug design
Neither path is narrower than the other. Both are rigorous, both publish in top journals, and both contribute to understanding human disease. The difference is in how you prefer to ask the question. And sometimes time…since you need to learn the skills of both chemistry AND biology to answer our research questions!
