About

Professor Hal Alper is a faculty member at the University of Texas at Austin in the Department of Chemical Engineering and the Institute for Cellular and Molecular Biology. His educational background includes a B.S. in Chemical Engineering from the University of Maryland at College Park and a Ph.D. in Chemical Engineering from the Massachusetts Institute of Technology. He has also completed postdoctoral research at the Whitehead Institute and Shire Human Genetic Therapies. His research focuses on applying synthetic biology techniques to develop more efficient strategies for producing industrially important and/or specialty chemicals. His work involves integrating metabolic engineering and synthetic biology to create sustainable solutions, including the valorization of waste resources for bioproduct production, bioremediation and upcycling of plastics, and the development of living materials with biological functionality. Professor Alper's research aims to engineer microbes and biological systems for industrial applications, emphasizing sustainability and environmental impact.

Research topics

• Computer Science
• Chemistry
• Chemical engineering
• Biochemical engineering
• Computational biology
• Biology
• Stereochemistry
• Data science
• Materials science
• Organic chemistry
• Pulp and paper industry
• Biotechnology
• Polymer chemistry
• Biochemistry
• Nanotechnology
• Composite material

Selected publications

• Space Biomanufacturing of Lactic Acid: Conceptual Design and Techno-Economic Analysis

  ChemRxiv · 2026-02-02

  articleOpen access

  Space biomanufacturing supports long-term missions by generating products on-site and thereby reducing costly resupply. Because the deployment cost is dominated by the mass of transported components and resources, the total mass becomes a key design driver. The total system mass is thus a critical factor that dictates its design; specifically, mass constraints require tight system integration and restrict the type of resources and equipment used. In this work, we present a computational framework to conduct design and techno-economic analysis of space biomanufacturing systems, using lactic acid production as an example. Lactic acid (LA) is a platform chemical that can be converted into polylactic acid (PLA), a biodegradable polymer with multiple applications, including materials for habitat construction. We use the Equivalent System Mass (ESM) metric as the key design metric that maps system components (e.g., energy, resources, equipment) to a common mass basis. Our analysis reveals that the preservation modality plays a key role in overall system mass primarily due to energy use. We also found that lyophilized cultures can reduce storage energy use by up to 99% compared to cryopreservation. By leveraging in-situ resource utilization, an 8-ton system could supply the PLA required for a representative lunar habitat design, while reducing logistical mass requirement by nearly 90% relative to launching all materials from Earth. In addition, we find that radiation-induced reductions in microbial yield can increase system mass by up to 28%. These findings highlight how a mass-centered approach can guide the design of modular, resource-efficient biomanufacturing systems for future space habitats.

  PublisherOA PDFDOI

• Bioproduction, bioprotection, and biocontainment in multi-kingdom microbial systems with 3D spatial control

  Biofabrication · 2026-03-23

  articleOpen access

  Abstract Engineered living materials (ELMs) are a class of hybrid materials that include engineered microbes encapsulated by a polymer matrix. The biotic and abiotic components define the ELMs design space and can be altered to improve performance and function. While current synthetic materials in the field display robust biocompatibility with both native and engineered living systems, we have a limited understanding of how to leverage three-dimensional (3D) form factors to spatially organize and control microbial dynamics within the material. Motivated by this knowledge gap, we employed extrusion-based 3D printing to fabricate multi-kingdom hydrogel constructs for the encapsulation of both single and multi-kingdom microbial systems. Core–shell cubic constructs enabled the spatial organization of a constitutive multi-kingdom system of levodopa (L-DOPA)-producing E. coli and betaxanthins (BXN)-producing S. cerevisiae . This spatial organization in 3D materials can introduce precise control over bioproduction, bioprotection, and biocontainment features that are critical to the efficacy of current ELMs. The relative spatial organization of the organisms, as well as the surface area-to-volume ratio were investigated to determine how these design elements impact microbial behavior (metabolite production, growth, expression, and cell distribution) over time. We demonstrated that F127-bis-urethane methacrylate (F127-BUM) core–shell geometries enable the hierarchical 3D printing of multi-kingdom constructs, offering customizable control over bioproduction, bioprotection, and biocontainment. With the optimization of these core–shell structures for continuous bioproduction, these ELMs could be deployed as compact and sustainable bioreactors in remote environments.

  PublisherDOI

• Real-time, <i>in situ</i> fluorescence and optical density measurements of liquid cultures in simulated microgravity

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-03-25

  articleOpen access

  Abstract As human space exploration expands to the Moon, Mars, and beyond, there is a growing need to study the effects of altered gravity on the microbial systems that we will bring with us for life support. Because spaceflight experiment opportunities are rare and resource-intensive, most space biology experiments are conducted using ground-based simulators. The most common microgravity simulator for microbial experiments, the rotating wall vessel, can approximate the low-shear and low-turbulence conditions that characterize microgravity. However, current designs do not allow for real-time measurement of growth or metabolic activity during rotation: experiments require destructive sampling or disruption of the microgravity simulation conditions. Here, we describe the development of an in situ spectroscopy system compatible with the Cell Spinpod rotating wall vessel, which enables measurement of both optical absorbance and fluorescence with high temporal resolution, producing growth curves similar to those from an off-the-shelf plate reader. These results are validated using two common microbial hosts: Escherichia coli and Saccharomyces cerevisiae . The Spinpod Optical System has the potential to diversify the types of microbiology experiments possible in simulated microgravity, allowing the measurement of not only growth curve parameters but also metabolic activity, gene expression, or community dynamics. It thus has the potential to improve the quality of experiments seeking to characterize microbial responses to spaceflight conditions.

  PublisherOA PDFDOI

• Asking the 5 W's for designing next‐generation bioprocessing

  AIChE Journal · 2026-04-27

  articleOpen accessSenior authorCorresponding

  Abstract Biotechnology is expanding beyond traditional, centralized fermentation and toward next‐generation bioprocessing paradigms that emphasize flexible deployment outside the laboratory with application‐specific performance. However, many bioprocesses fail to translate beyond proof‐of‐concept into industrially viable systems because early design decisions are often misaligned with economic, operational, and temporal constraints. In this perspective, we propose the systematic use of the traditional “5 W” questions (Who, What, Where, Why, and When) as a unifying framework for guiding the design of next‐generation bioprocesses. Rather than serving as a checklist, the 5 W's function as a design lens to interrogate host selection, yield constraints, deployment context, purpose, and timing of bioprocesses. Through examples spanning conventional and non‐conventional bioprocesses, we illustrate how neglecting these considerations can yield technically elegant yet operationally irrelevant systems. We argue that early qualitative framing through the 5 W's can reduce costly redesign and accelerate translation of next‐generation biotechnology into industrially relevant applications.

  PublisherDOI

• Applying a vacuum ultraviolet detector for liquid chromatography: Simultaneous analysis of four organic acids and four carbohydrates in a fermentation process

  Journal of Chromatography B · 2026-01-08 · 1 citations

  articleSenior authorCorresponding
  PublisherDOI

• Engineering the yeast Yarrowia lipolytica for biomanufacturing

  Current Opinion in Biotechnology · 2026-03-10 · 1 citations

  articleOpen accessCorresponding

  The oleaginous yeast Yarrowia lipolytica has become a prominent cell factory for industrial biotechnology due to its robust physiology and metabolic versatility. The genetic toolkits have advanced from early approaches based on nonhomologous end joining to precise CRISPR editing and, recently, to high-throughput genome engineering. Genome-scale metabolic modeling, ‘omic data, and other systems metabolic engineering approaches further accelerate the development of Y. lipolytica strains for biomanufacturing. This review summarizes recent progress in the metabolic engineering of Y. lipolytica, spanning genome editing strategies, systems-level approaches, and representative industrial and biotechnological applications with commercial potential. Together, these advances position Y. lipolytica as a leading microbial workhorse for biomanufacturing. • Y. lipolytica gains recognition in industrial and academic biotechnology. • High-throughput and systems approaches streamline pathway optimization. • Diverse high-titer products highlight strong commercial promise. • Remaining challenges and future directions are critically discussed.

  PublisherDOI

• Genome-scale prediction of gene ontology from mass fingerprints reveals new metabolic gene functions

  Life Science Alliance · 2025-08-22

  articleOpen access

  Mass-based fingerprinting can characterize microorganisms; however, expansion of these methods to predict specific gene functions is lacking. Therefore, mass fingerprinting was developed to functionally profile a yeast knockout library. Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) fingerprints of 3,238 Saccharomyces cerevisiae knockouts were digitized for correlation with gene ontology (GO). Random forests and support vector machine (SVM) algorithms assigned GO terms with average AUC values of 0.994 and 0.980, respectively. SVM was the best predictor with average true-positive and true-negative rates of 0.983 and 0.993, respectively. To test predictions of unknown gene functions, the dataset of uncharacterized yeast gene knockouts was evaluated based on SVM scores, and new functions were suggested for 28 corresponding genes. Metabolomics analysis of two knockouts (YDR215C and YLR122C) of uncharacterized genes predicted to be involved in methylation-related metabolism showed altered intracellular contents of methionine-related metabolites. Increased S-adenosylmethionine in YDR215C indicated that this strain shows potential as a chassis for bioproduction of methylated compounds. This study demonstrates that fingerprinting can generate large functional datasets for improved machine learning–based gene function prediction.

  PublisherOA PDFDOI

• Developing a Yarrowia lipolytica platform for conversion of mannitol-containing waste streams

  Bioresource Technology · 2025-08-19 · 1 citations

  articleOpen accessSenior author

  Yarrowia lipolytica holds significant promise for bioconversion of renewable feedstocks, yet its capacity to efficiently assimilate mannitol, a major carbon source in olive mill wastewater (OMWW), remains limited. Here, we conducted adaptive laboratory evolution (ALE) under mannitol-exclusive conditions using four different Y. lipolytica strains followed by integrative genetic and transcriptomic analyses. These strains exhibited markedly enhanced mannitol assimilation and growth of upwards of 22-fold increase in utilization. Whole-genome sequencing and reverse engineering revealed that a point mutation in STA1 (A403T), encoding glucan 1,4-α-glucosidase, contributed to improved growth. Transcriptomic analysis showed upregulation of MFE2, associated with peroxisomal β-oxidation, and downregulation of DGA1, a key gene for triacylglycerol synthesis, indicating a systems-level metabolic shift that favors energy mobilization over storage lipid accumulation. When cultivated in OMWW-derived media, the evolved strains achieved two-fold higher lipid production compared to its parental strain from mannitol and simultaneously reduced the chemical oxygen demand (COD) by 90 %. Taken together, these findings expand the genetic and regulatory landscape underlying mannitol assimilation in Y. lipolytica and demonstrate the potential of evolved strains for bioconversion of waste-derived substrates into valuable biochemicals.

  PublisherDOI

• Plastic degradation by enzymes from uncultured deep sea microorganisms

  The ISME Journal · 2025-01-01 · 5 citations

  articleOpen access

  Polyethylene terephthalate (PET)-hydrolyzing enzymes (PETases) are a recently discovered enzyme class capable of plastic degradation. PETases are commonly identified in bacteria; however, pipelines for discovery are often biased to recover highly similar enzymes. Here, we searched metagenomic data from hydrothermally impacted deep sea sediments in the Guaymas Basin (Gulf of California) for PETases. A broad diversity of potential proteins were identified and 22 were selected based on their potential thermal stability and phylogenetic novelty. Heterologous expression and functional analysis of these candidate PETases revealed three candidates capable of depolymerizing PET or its byproducts. One is a PETase from a Bathyarchaeia archaeon (dubbed GuaPA, for Guaymas PETase Archaeal) and two bishydroxyethylene terephthalate-hydrolyzing enzymes (BHETases) from uncultured bacteria, Poribacteria, and Thermotogota. GuaPA is the first archaeal PETase discovered that is able to depolymerize PET films and originates from a specific enzyme class which has endowed it with predicted novel structural features. Within 48 h, GuaPA released ~3-5 mM of terephthalic acid and mono-(2-hydroxyethyl) terephthalate from low crystallinity PET. PET co-hydrolysis containing GuaPA and one of the newly discovered BHETases further improves the hydrolysis of untreated PET film by 68%. Genomic analysis of the PETase- and BHETase-encoding microorganisms reveals that they likely metabolize the products of enzymatic PET depolymerization, suggesting an ecological role in utilizing anthropogenic carbon sources. Our analysis reveals a previously uncharacterized ability of these uncultured microorganisms to catabolize PET, suggesting that the deep ocean is a potential reservoir of biocatalysts for the depolymerization of plastic waste.

  PublisherOA PDFDOI

• Emerging hosts for metabolic engineering

  Metabolic Engineering · 2025-10-21

  editorial1st authorCorresponding
  PublisherDOI

Recent grants

• Engineering Molecular Transport Proteins for Improved Xylose Uptake in Yeast

  NSF · $361k · 2012–2015

• Collaborative Research: Continuous Biomanufacturing using Decoupled Growth and Production Stages for Efficient Production and Recovery

  NSF · $313k · 2022–2025

• Collaborative Research: A New Yeast Biomanufacturing Platform for Making High-value Products from Oils and Fats

  NSF · $302k · 2020–2024

• NIH Grant R01GM090221

  NIH · $513k · 2013

Frequent coauthors

• Gregory Stephanopoulos

  Massachusetts Institute of Technology

  26 shared

• Shuo‐Fu Yuan

  18 shared

• James M. Wagner

  The University of Texas at Austin

  17 shared

• Leqian Liu

  University of California, San Francisco

  16 shared

• Sun‐Mi Lee

  Korea Institute of Science and Technology

  15 shared

• Simon d’Oelsnitz

  The University of Texas at Austin

  13 shared

• Sierra M. Brooks

  The University of Texas at Austin

  13 shared

• Joel F. Moxley

  13 shared

Labs

• Alper LaboratoryPI

  Not provided

Education

• B.S., Chemical Engineering

  University of Maryland, College Park

  2002

• Ph.D., Chemical Engineering

  Massachusetts Institute of Technology

  2006

Awards & honors

• American Association for the Advancement of Science fellow (…
• Andreas Acrivos Award for Professional Progress in Chemical…
• National Academy of Inventors fellow (2019)
• Edith and Peter O'Donnell Award in Engineering – TAMEST (201…
• Allan P. Colburn Award for Excellence in Publications by a Y…