Graduate Spotlight: Kausar Samli

Kausar SamliExpected Graduation: Winter 2012
Degree Objective: Ph.D. in Biochemistry
Other Degrees: M.S. in Chemistry, B.S. in Biochemistry

Kausar Samli radiates ambition when discussing his research and future plans. Fittingly, his drive to confront global problems arises from personal motivation.

“I have friends and family scattered around the world, and many don’t have access to technology and services that we have access to, like modern health care or certain biomedical procedures,” said Samli, a biochemistry doctoral student at the University of Georgia.

Having lived in Asia, the Middle East and Europe, Samli refers to himself as a “global nomad.” His background allows him to understand diverse cultural perspectives and inspired him to achieve positive social change with his research.

“Beyond just the research and design, I want to develop and translate my projects into efforts that have societal impact,” he said.

His ideas are exemplified by his participation on an interdisciplinary team at Singularity University’s Graduate Studies Program. At Singularity University, he learned how to think broadly about addressing the problems of one billion people.

“Increasingly, the trend for solving today’s and tomorrow’s challenges requires interdisciplinary solutions,” said Samli. “We have to merge multiple disciplines to develop solutions to global challenges.”

Samli pulls together his interdisciplinary approach to global challenges at UGA’s Complex Carbohydrate Research Center. He and his doctoral adviser, Professor Robert Woods, in collaboration with Lori Yang, CSO of Glycosensors and Diagnostics, LLC, design biomolecules by combining protein engineering with computer simulations capable of modeling complex systems. The computer simulations allow them to create models showing how a protein interacts with its environment on a macromolecular level.

Samli’s dissertation research focuses on using engineered proteins to detect the presence or absence of certain glycans, which are complex carbohydrate structures. Glycans are found on cell surfaces and proteins, where they are involved in many diverse cellular processes, including cell signaling and immune system responses.

According to Samli, glycans “decorate” the exterior of proteins in a process known as glycosylation. Detecting these glycosylated proteins – called glycoproteins – in complex mixtures is the crux of his research, because glycoproteins can reveal information about the health or state of the organism or system.

“We’re reengineering existing enzymes and proteins to improve their affinity for carbohydrate structures, their ability to detect glycan bearing proteins known as glycoproteins,” said Samli.

In other words, these novel reengineered biomolecules can be used as sophisticated biosensors, capable of detecting disease biomarkers or monitoring bioprocesses.

“We can, at some point, develop biomolecules that recognize disease biomarkers,” said Samli. “For example, in certain cancers, the glycans are different than in non-cancer, healthy cells and its glycoproteins.”

These engineered proteins put Samli, Woods, Yang and the Complex Carbohydrate Research Center on the forefront of the burgeoning industry of biomedical drugs, called therapeutic biologics.

“Recently, there’s been an increasing shift in the pharmaceutical industry from developing small molecule drugs to developing therapeutic biologics,” said Samli. “Biologics are made using cellular machinery – they are grown in bioreactors using specialized cells instead of being chemically synthesized.”

Samli said biologics are quickly becoming a popular alternative for pharmaceutical companies. In the last five years, therapeutic biologics have grown from 10 percent to 28 percent of the new drugs approved by the Food and Drug Administration.

Furthermore, as therapeutic biologics drive the growth of new drugs, glycosylated proteins are fueling the proliferation of biologics. More than two-thirds of recently approved biologics are glycosylated. Glycosylated biologics have several advantages over other drugs, including improved activity, pharmacokinetics, clearance, and immunogenicity.

However, the complex nature of producing and harvesting biologics is filled with variables. Glycoproteins can take a variety of forms, and each glycoprotein may have numerous variations, called glycoforms. Minor changes to the way the therapeutic glycoprotein is produced can alter its glycoform distribution, and a pharmaceutical company must be certain it produces a consistent product.

“Tiny variations in making biologics can change the glycoform of the glycoprotein,” said Samli. “You have to narrow it down and identify the correct form before you harvest it, and even then you have to make sure the protein has the desired structure and function.”

Samli explains that the pharmaceutical industry must be extremely careful about how it grows biologics, especially glycosylated proteins. Glycosylated biologics have to be consistent in their structure and function. A change in a protein’s glycoform can affect drug efficacy or, even worse, could lead to a drug with adverse health effects.

“Scientists in the pharmaceutical industry need to know when to harvest glycosylated biologics, that is, they have to harvest it when it has the right glycosylated structure while maximizing overall yield,” he said. “We have to have tools, novel tools, to reaffirm the correct glycan structure on biologics. This is a growing need in bioprocess monitoring when growing and harvesting biologics.”

The potential of therapeutic biologics to confront a wide array of global health issues assures Samli his research will be rewarded.

“I want to be at the forefront of cutting edge research and development and commercialize these biotechnologies in order to advance science and technology policy development and implementation on a global scale to address global grand challenges,” said Samli.

By merging computational modeling and protein engineering to develop novel biotech tools, Samli’s goal to improve the lives of one billion people closes in on reality.

Photograph by Nancy Evelyn; Story by Ben Benson