Investigating molecular and cellular basis of whole-organism physiology 

The type of research questions that we find interesting and pursue in the Delventhal lab are very diverse, but ultimately are all routed in the goal of uncovering the molecular mechanisms (which genes are expressed, how cells communicate, etc.) that contribute to biological processes that manifest at the level of a whole organism (such as behavior, survival, development, immunity, metabolism, etc.). We currently have several projects within two main areas of research: (1) Traumatic Brain Injury (TBI) and (2) ER Membrane Protein Complex (EMC), as described below.

Traumatic Brain Injury (TBI) research projects 

Differential outcomes of repetitive TBI

Preliminary data from our lab suggests that there are different short- and long-term outcomes from a single, severe TBI, when compared to a less severe, repetitive injury. We are interested in further characterizing the differences in physiological, behavioral, and molecular changes triggered by repeated trauma vs. a single TBI event. We are also more broadly interested in comparing different injury paradigms to uncover common and unique injury outcomes.

Impact of TBI on sleep behavior and oxidative stress

Preliminary data from our lab suggests that flies initially exhibit more fragmented sleep in the first 1-2 weeks post-TBI sleep, and then eventually display increased sleep 2-4 weeks post-TBI. Given the known link between sleep and clearance of reactive oxygen species (ROS) (Hill et al. PNAS 2018), we are now investigating whether TBI induces oxidative stress responses and whether manipulation of oxidative stress response genes may impact TBI outcomes.

Sex-specific outcomes following TBI

Some recent Drosophila studies have examined male and female TBI outcomes separately*, yet the majority of published research (including our own prior research) focuses on males, or mixed populations. We are interested in examining TBI-induced changes that are unique to female flies, and whether there may be treatments to mitigate the effects of TBI that are more successful in female flies.

Interaction between metabolism and TBI

We have discovered that a single, severe TBI leads to changes in metabolic function that resolves mid-term (a few weeks following TBI). Dietary changes can also ameliorate some, but not all, of the TBI-induced outcomes. (see Delventhal et al Scientific Reports 2022) We are interested in identifying the metabolic regulatory pathways that may be altered in response to the TBI.

Endoplasmic Reticulum (ER) Membrane protein Complex in a multicellular organism

Glial cell specific role for EMC4 in adulthood

Preliminary data from our lab suggests that glial-specific knockdown of EMC4 leads to severely shortened adult lifespan, locomotor defects, and protein aggregation. We are investigating the molecular causes of this and whether the damage from loss of EMC4 is acute onset during adulthood, or derives from loss of EMC4 during development prior to eclosion as adult flies.

Glial cell specific role for EMC4 during development

Preliminary data from our lab suggests that glial-specific knockdown of EMC4 leads to a longer developmental period. We are currently investigating during which phase of the fly lifecycle the delay occurs, and whether loss of glial EMC4 impacts other developmental processes, such as larval behavior.

Role of EMC4 in other cell types

Given the striking results from knockdown of EMC4 in glial cells, we are interested in whether EMC4 may play a similarly essential role in other types of cells? Or whether loss of EMC4 in other cell types is perhaps not as detrimental?

*image adapted from Buchon et al Nat Rev Immuno 2014