Qili Liu, PhD

We are bombarded with choices, seemingly at all hours of the day. Dr. Qili Liu PhD, an Assistant Professor in the Department of Anatomy at UCSF, studies how we make decisions. Every decision that we make, throughout the day, can be influenced by myriad factors including cultural preferences, social biases and learned behaviors. Rarely do we consider the internal, biological factors that are at play. Yet, these internal factors can powerfully direct our decision-making process. Specifically, Dr. Liu studies the complex neuronal mechanisms underlying food selection. To what extent are food choices determined by our biological needs? Is there an innate hunger for specific nutrients that drives our decision-making process? Dr. Liu explores these questions. 

Over the past century, there has been remarkable research regarding energy metabolism – the means by which food is processed into sources of energy that power the brain, our muscles and other complex tissues. Indeed, scientists have created a ‘metabolic map’ that describes the biology of energy storage, utilization and distribution throughout the body, work for which numerous Noble Prizes have been awarded over the years. The metabolic map can be considered one of the most remarkable achievements of the last century of biological science. Yet, mysteries remain!  Currently, scientists acknowledge that very little is known regarding how an organism “decides” which nutrients to consume in the first place. Food consumption is essential for survival. But mechanisms that are responsible for sensing specific nutrients in sources of food remain largely unknown.   

Dr. Liu hopes to establish an understanding of nutrient specific appetite– the urge to search for and consume individual nutrients, such as salt or protein. To make progress on this fundamental question, her lab uses Drosophila (fruit flies) as a model organism with powerful tools of molecular biology and genetics to offer. Will it be possible to determine the molecular signals and brain circuits that control nutrient specific appetite? Liu believes so and Drosophila may hold a key!  

Nearly a century ago, Dr. Curt Richter did primary research on salt specific appetite and proposed that animals have specific appetites for diverse nutrients. Currently, it is well-established that animals have a drive to consume sodium (sodium appetite), protein (a protein appetite), as well as sugar (sugar appetite), and it is debated whether there may also be a sugar appetite. How many appetites are there? How is an appetite created in biological terms and how does an animal know when this appetite has been satisfied? How do different types of appetites interact with each other to ensure that a balanced diet is consumed? At the root of these questions is the fact that appetite is a motivated behavior. The concept of motivation can be divided into need-based factors (a need for salt to survive) and non-need-based factors (e.g., stress, social and emotional facts, or learned events). Ultimately, motivation serves to energize behavior in pursuit of a goal. This is something all animals share to fulfill basic needs, including food, water, sleep, etc.   

This gets us back to some basic questions: how is appetite motivation created and how is it satisfied?   

The experimental foundation of Liu’s lab is the fruit fly Drosophila melanogaster. This model organism has been used for decades to identify the genetic basis of diverse biological phenomena ranging from the determinants of an animal body plan (head, body, appendages) to the cellular mechanisms responsible for taste. A fly’s brain contains only ~100,000 neurons - compared to human’s ~100 billion - making it easier to identify the ones that are active when a fly behaves in a particular way. Liu controls the fruit fly diet, eliminating one nutrient at a time, and quantifies the behavioral consequences of food selection. For example, a fly that is deprived of dietary protein will later be exposed to two food options: one high in protein and the other low. The researcher then quantifies the food preference to determine if it prefers the high protein content food. This can be done on a large scale, testing thousands of flies across many different food preference paradigms, each fly potentially harboring a manupulation that specifically alters just one gene. Ultimately, Liu is looking to discover the molecular pathways that are necessary for the acquired food preference. As Liu and her lab progress, they hope to uncover a molecular and genetic roadmap for understanding motivated animal behavior related to nutrient specific appetites.   

What other fundamental processes might emerge? One of the founding principles of the field of Physiology is “Homeostasis”. As originally defined by Walter Cannon in the early 1900s, the term homeostasis refers to the ability of a cell, or a cellular system to respond to a perturbation and maintain functionality within a defined, biologically relevant range. Walter Cannon originally described homeostasis when referring to the control of human heart rate. One of the most mysterious aspects of biological system under homeostatic control is the ‘set point’ to which the system always returns. A set point is intuitively similar to setting the temperature on a thermostat to keep the temperature within a specific range despite changes in outside temperature over the course of a day. What is the set point for the intake of a given nutrient? How is that established using molecules and cells within the nervous system? This is a complete mystery, but Liu and her lab are making progress! Female flies naturally eat more protein compared to males. When females are pregnant, they need even more protein! Taking advantage of the sex- and mating status-dependent variabilities in protein intake, Liu’s lab has discovered novel molecular pathways that participate in a protein appetite set point.   

There is a century of research demonstrating a fundamental conservation of basic biology that connects fruit flies to humans. Without a doubt, food preferences will differ across organisms. The neural circuitry in flies and humans are also very different, but the molecular pathways, and the homeostatic foundations of animal physiology, are likely to be conserved among animals. We know now that protein specific appetite can not only lead flies to eat protein but stop them from seeking out sugar. This suggests there is a competition between different types of hunger. It could help us understand how to make sure one kind of appetite does not dominate over others in humans and  

lead to health issues such as obesity. If food intake set points can be defined and rationally manipulated, these could become novel points of therapeutic intervention, not unlike changing the temperature on a thermostat, but controlling motivated behavior around food consumption and metabolism.   

Liu planned to pursue a career as a high school teacher as her parents wished, promoting her to attend college to become a teacher. But, what really got her excited wasn’t teaching textbook information, she was fascinated by how the information within these textbooks was generated in the first place. The idea of becoming a scientist, seemed like a dream job, beautifully merging the adventure of exploratory research and the process of education. In her sophomore year of undergraduate work, Liu studied the reproductive strategies of a wild plant species, how they adapt to their environment, and how they take advantage of their environment. This experience led her to pursue a PhD at the Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, studying stem cell maintenance in plants. Then, following her PhD, becoming enthralled by circadian rhythms that are common to all organisms, Dr. Liu moved to the United States to work in Dr. Mark Wu’s laboratory at the Johns Hopkins University. It was there that Liu jumped from plants to animals and ultimately to neuroscience. This path is unusual, but not entirely unique for scientists. Discoveries in one area of biology can lead to new insights that inform other seemingly disparate areas. Liu has a passion for the biology of circadian rhythms, which led her to work with Drosophila and feeding behavior, which is influenced by circadian signals within the brain. While developing tools to better understand how behaviors are controlled by brain circuitry, she veered off into the area of feeding regulation. Her progress in protein specific appetite landed her a recent faculty position at UCSF.  

More about the Liu Lab