Siddiq Lab

Department of Human Genetics
University of Utah

Molecular evolution of proteins & Pathways

Change is inevitable, and
even the most fundamental processes evolve.

We combine approaches from molecular biology, phylogenetics, and biochemistry to study this evolution, with a focus on metabolic enzymes and pathways.

Image: The first phylogeny seen in Charles Darwin's notes.

Constraint and innovation in evolution

Our research

We investigate how evolution shapes — and becomes shaped by — the mechanistic links between genotype, phenotype, and fitness. Our work explores genotype-phenotype-fitness relationships and their evolution in two frameworks: moonlighting functions of proteins and drift in the genetic architecture of pathways amidst constraint.

Protein moonlighting

How do life's most conserved molecules evolve additional functions while retaining the ones that made them essential?

A model (right): The ubiquitous housekeeping enzyme GAPDH has been discovered to have roles beyond glycolysis in multiple species. We use evolution to understand how these biochemically distinct functions arise, coexist and covary.

Pathway drift

How do molecular systems that make life possible continuously change in architecture while meeting the demands of necessity?

Divergent architecture (left): Core pathways, including glycolysis, have conserved inputs (sugar) and outputs (energy). Yet, gene content, protein levels, and enzyme efficiencies all continue to (co)evolve.

Our Lab

Our principles

The co-creation of knowledge is a uniquely human joy, and the underlying creative process is a personal, formative experience for each individual. Our lab is committed to creating an environment in which every individual feels concurrently supported, challenged, and mentored towards defining and pursuing their visions of excellence. The science we practice today has been made possible because of the contributions of people from every walk of life; the most impactful science of tomorrow will be shaped by scientists from every walk of life, too.

Our goal is to foster an environment that emphasizes rigorous inquiry and compassionate communication to support both the science and the scientist and, in turn, strengthen our practice of craft and of community.

Lab News

Celine Mayer begins her scientific journey in the Siddiq Lab! Celine is an alum of the University of Utah and its NCAA champion ski team.

One published and one pre-printed paper from Mo's postdoc! Check them out:
1. Deep homology and design of proteasome chaperone proteins in Candidozyma auris
2. cis- and trans-regulatory factors contributing to divergent activity of the TDH3 promoter in Saccharomyces yeast

The doors to the Siddiq Lab open with Niraja Bhachech joining as a founding member! We could not be more excited to be here.