About Soares lab: our 2 strategies towards Biological research

About twenty years ago Donald Rumsfeld, the then US secretary of state for defense, attended a briefing about the war in Iraq and said : ‘There are known knowns. There are things we know that we know. There are known unknowns. That is to say, there are things that we now know we don't know. But there are also unknown unknowns. There are things we do not know we don't know.’ He was mocked mercilessly in the media since most people thought the statement was gibberish. Although I have never been a Rumsfeld fan, as a neuroscience graduate student at the time I loved the idea. There are things that we don't even know that we don't know? (As it turns out, the concept of the unknown unknown existed long before Donald Rumsfeld shared it, and apparently NASA has been using it for decades in risk assessment).

Much of our scientific research is based on investigating known unknowns. Researchers develop hypotheses, then design experiments to test these hypotheses. Scientists (and grant review panels) expect that a result will be within a range of known possibilities. This is a well established, and very fruitful approach to understand nature. I certainly use it in my lab and courses. However, there is a complimentary approach known unknowns science: a discovery based "unknown unknowns" methodology. Data mining for example, is a type of discovering the"unknown unknowns". This exploratory science is more descriptive than predictive, focuses more on curiosity and tends to investigate a problem which is not clearly defined. It can happen when a scientist first encounters a natural phenomenon. There is a lot in the literature about both scientific strategies, and many philosophers explored their differences and history (check this link if you are interested).

I employ both approaches in my laboratory. And, in our case, when I mean discovery based exploratory research, I really mean field work, where we investigate extreme environments (such as caves) and their endemic animals. How many ways are there to put a nervous system together?

Our hypothesis driven research:

The understanding of the neural underpinnings of clinical manifestations of maladaptive behaviors has been a major goal of psychiatry, neuroscience, and medicine. Additionally, the permeance of maladaptive behaviors over evolutionary time has been a conundrum. Maladaptations occur when a circuit fails to generate the adapted natural behavior which increases chances of survival (and therefore future possible mating). One of the common causes of maladaptations is the appearance of stressful environmental challenges during development. But given the intricate nature of maladaptive behavior, only a multifaceted, long perspective approach, can inform new clinical interventions that rely on plastic circuit changes that can ameliorate aberrant neural responses. Interdisciplinary strategies in multiple time scale frameworks help advance the field toward improved diagnosis and treatment in ways that single, static, disciplines cannot. Likewise, simple neural circuits models are essential to the understanding of the mechanisms underlying maladaptive behaviors at a novel cellular level. Structural and functional neuronal development unfolds due to the ongoing interplay between genes and the local environment, making early development a critical period for the setup of neuronal circuits that will govern behaviors for the rest of the lifetime of an individual. It has been well documented that many maladaptive behaviors, such as psychiatric disorders, not only appear during childhood but also run in families, also suggesting genetic roots to circuit assembly (see Tepfer et al., 2021 for latest example). Many aspects of brain structure are highly heritable and genetic factors tightly control the morphological variability of neurons, even though no specific gene that determines aberrant circuits has been unambiguously identified for many mental disorders. Less is known about the impact the environment has in circuit connectivity and neuronal morphology, of the brain areas that are more susceptible to developmental cues. Phenotypic plasticity during development has been argued to be the ancestral character state for most if not all traits (see Fusco and Minelli, 2010 and Price et al., 2003 for reviews). Evolutionary-developmental (evo-devo) biologists argue that developmental plasticity plays the pivotal role in evolution and can drive phenotypic change via canalization. The deciphering of neuronal ontogenetic changes is necessary for understanding phenotypic changes of behavior over time (heritability).

Could natural selection and individual development help explain a host of mental states, and intergenerational continuity of maladaptive behavior? Natural selection is a blind process constrained by chance, trade-offs, probability, and changing environments. For this reason, adaptation and maladaptation are two sides of the same coin and should not be studied independently. The logic of maintaining adaptive behaviors that enhance fitness is self-evident. The significance of evolutionary shaping of the neurobiology that leads to maladaptive behaviors, however, are less clear. Unlike physical diseases, mental illness often has an onset early in the life of the individual, making the reproductive disadvantage considerable. The work in our lab is establishes a new model system of two species that bridges the gap in our understanding of how severe individual experiences during development can lead to maladaptive neuronal morphologies and behaviors over generations, perhaps via epigenetic mechanisms (for review on human behavior see Gartstein and Skinner, 2018, Lester et al., 2022).

Our discovery based exploratory research:

Why extreme environments? Our laboratory is interested in how animals survive and even strive in extreme environments. Extreme environments such as caves, are closely associated with phenotypic changes. Accommodation of phenotypic variation by developmental systems enables animals to use the footprint of the stressful event (such as cave colonization) as a driver for transgenerational effects. Adaptation to extreme environments is mediated through a wide variety of pressures. We are ultimately interested in determining: 1) Why do animals colonize extreme environments? 2) How common is convergent evolution in extreme environments? 3) How do physicochemical characteristics shape macroevolutionary processes? 6) how can we make basic research on extremophiles applicable to solving major scientific challenges ?

Why caves? Because all cave animals are derived from surface animals, those of which are often extant and accessible, we are able to determine the various ways in which physiology and behavior can respond to adaptive pressure. In other words, we have a window into the extent in which phenotypes can be pushed. Further, the accumulation of phenotypically neutral genetic variation is common evolutionary mechanism that leads to change, and caves promote the phenotypic expression of this variance, whether behaviorally, physiologically or morphologically. Since we often don't know what we are going to discover, our research program collaborates with laboratories from multiple disciplines, including population and community ecology, evolutionary biology, conservation biology, biogeography, systematics, population genetics, phylogenetics, statistics, astrobiology and genomics.

Biospeleology has a remarkable potential to inform many aspects of modern biology, including disease (eg. SARS-CoV-2).